Membrane Components and Structure structure was proposed in 1935 by Hugh Davson

and James Danielli; it was based on the

A cell’s plasma membrane defines the cell,
“railroad track” appearance of the plasma
outlines its borders, and determines the nature
membrane in early electron micrographs. They
of its interaction with its environment (see Table
theorized that the structure of the plasma
8.1 for a summary). Cells exclude some
membrane resembles a sandwich, with protein
substances, take in others, and excrete still
being analogous to the bread, and lipids being
others, all in controlled quantities. The plasma
analogous to the filling. In the 1950s, advances
membrane must be very flexible to allow certain
in microscopy, notably transmission electron
cells, such as red blood cells and white blood
microscopy (TEM), allowed researchers to see
cells, to change shape as they pass through
that the core of the plasma membrane
narrow capillaries. These are the more obvious
consisted of a double, rather than a single, layer.
functions of a plasma membrane. In addition,
A new model that better explains both the
the surface of the plasma membrane carries
microscopic observations and the function of
markers that allow cells to recognize one
that plasma membrane was proposed by S.J.
another, which is vital for tissue and organ
Singer and Garth L. Nicolson in 1972.
formation during early development, and which
later plays a role in the “self” versus “non-self” The explanation proposed by Singer and
distinction of the immune response. Nicolson is called the fluid mosaic model. The
model has evolved somewhat over time, but it
Among the most sophisticated functions of the
still best accounts for the structure and
plasma membrane is the ability to transmit
functions of the plasma membrane as we now
signals by means of complex, integral proteins
understand them. The fluid mosaic model
known as receptors. These proteins act both as
describes the structure of the plasma
receivers of extracellular inputs and as
membrane as a mosaic of components—
activators of intracellular processes. These
including phospholipids, cholesterol, proteins,
membrane receptors provide extracellular
and carbohydrates—that gives the membrane a
attachment sites for effectors like hormones and
fluid character. Plasma membranes range from
growth factors, and they activate intracellular
5 to 10 nm in thickness. For comparison, human
response cascades when their effectors are
red blood cells, visible via light microscopy, are
bound. Occasionally, receptors are hijacked by
approximately 8 µm wide, or approximately
viruses (HIV, human immunodeficiency virus, is
1,000 times wider than a plasma membrane.
one example) that use them to gain entry into
The membrane does look a bit like a sandwich
cells, and at times, the genes encoding
(Figure 8.2).
receptors become mutated, causing the process
of signal transduction to malfunction with
disastrous consequences.

8.1.1 Fluid Mosaic Model

The existence of the plasma membrane was

identified in the 1890s, and its chemical
components were identified in 1915. The
principal components identified at that time
were lipids and proteins. The first widely
accepted model of the plasma membrane’s Figure 8.2 The fluid mosaic model of the plasma
membrane describes the plasma membrane as The main fabric of the membrane is composed
a fluid combination of phospholipids, of amphiphilic phospholipid molecules. Recall
cholesterol, and proteins. Carbohydrates from chapter 4 that a phospholipid is a
attached to lipids (glycolipids) and to proteins molecule consisting of glycerol, two fatty acids,
(glycoproteins) extend from the outward-facing and a phosphate-linked head group (Figure
surface of the membrane. 8.3) . The hydrophilic “head” of these molecules
are in contact with the aqueous fluid both
The principal components of a plasma
inside and outside the cell. The hydrophobic
membrane are lipids, proteins, and
“tails” face each other in the inside of the
carbohydrates. The lipids include phospholipids
bilayer. Therefore, phospholipids form an
and cholesterol Proteins either float in the
excellent two-layer cell membrane that
bilayer or are attached to one side or the other
separates fluid within the cell from the fluid
of it. Carbohydrate chains are attached to the
outside of the cell (Figure 8.2).
proteins and lipids on the outside surface of the
membrane. The proportions of proteins, lipids, The amphipathic nature of phospholipids is vital
and carbohydrates in the plasma membrane to the structure of a plasma membrane
vary with cell type, but for a typical human cell, because, in water, phospholipids automatically
protein accounts for about 50 percent of the become arranged with their hydrophobic tails
composition by mass, lipids account for about facing each other and their hydrophilic heads
40 percent of the composition by mass, with the facing out. In this way, they form a lipid bilayer
remaining 10 percent of the composition by —a barrier composed of a double layer of
mass being carbohydrates. phospholipids that separates the water and
other materials on one side of the barrier from
Phospholipids
the water and other materials on the other side
(Figure 8.4 top). In fact, phospholipids heated in
an aqueous solution tend to spontaneously
form small spheres or droplets called micelles,
with their hydrophilic heads forming the
exterior and their hydrophobic tails on the
inside (Figure 8.4 bottom).

Fig
ure 8.3 This phospholipid molecule is composed
of a hydrophilic phosphate group head and two
hydrophobic fatty acid tails.
 regions. This arrangement of regions of the
protein tends to orient the protein alongside
the phospholipids, with the hydrophobic region
of the protein adjacent to the tails of the
phospholipids and the hydrophilic region or
regions of the protein protruding from the
membrane and in contact with the cytosol or
extracellular fluid.

Figure 8.4 In an aqueous solution,

phospholipids tend to arrange themselves with
their polar heads facing outward and their
hydrophobic tails facing inward. At high
concentrations, they form a bilayer, such as the
plasma membrane of cells (top). At lower
concentrations, they form micelles (bottom).
(Credit: modification of work by Mariana Ruiz Figure 8.5 Integral membranes proteins may
Villareal) have one or more alpha-helices that span the
membrane (examples 1 and 2), or they may
Proteins
have beta-sheets that span the membrane
Proteins make up the second major component (example 3). (credit: “Foobar”/Wikimedia
of plasma membranes. Integral proteins are, as Commons)
their name suggests, integrated completely into
Peripheral proteins are found on the exterior
the membrane structure, and their hydrophobic
and interior surfaces of membranes, attached
membrane-spanning regions interact with the
either to integral proteins or to phospholipids.
hydrophobic region of the the phospholipid
Peripheral proteins, along with integral proteins,
bilayer (Figure 8.2). Single-pass integral
may serve as enzymes, as structural
membrane proteins usually have a hydrophobic
attachments for the fibers of the cytoskeleton,
transmembrane segment that consists of 20–25
or as part of the cell’s recognition sites. These
amino acids. Some span only part of the
are sometimes referred to as “cell-specific”
membrane— associating with a single layer—
proteins. The body recognizes its own proteins
while others stretch from one side of the
and attacks foreign proteins associated with
membrane to the other, and are exposed on
invasive pathogens.
either side. Since they cross the membrane,
these are often called transmembrane proteins. Carbohydrates

Some complex integral proteins are composed Carbohydrates are the third major component
of up to 12 segments, which are extensively of plasma membranes. They are always found
folded and embedded in the membrane (Figure on the exterior surface of cells and are bound
8.5). This type of protein has a hydrophilic either to proteins (forming glycoproteins) or to
region or regions, and several hydrophobic lipids (forming glycolipids) (Figure 8.2). These
carbohydrate chains may consist of 2–60 some monocytes and central nervous system
monosaccharide units and can be either straight cells. The hepatitis virus attacks liver cells.
or branched. Along with peripheral proteins,
These viruses are able to invade these cells,
carbohydrates form specialized sites on the cell
because the cells have binding sites on their
surface that allow cells to recognize each other.
surfaces that are specific to and compatible
These sites have unique patterns that allow the
with certain viruses (Figure 8.6). Other
cell to be recognized, much the way that the
recognition sites on the virus’s surface interact
facial features unique to each person allow him
with the human immune system, prompting the
or her to be recognized. This recognition
body to produce antibodies. Antibodies are
function is very important to cells, as it allows
made in response to the antigens or proteins
the immune system to differentiate between
associated with invasive pathogens, or in
body cells (called “self”) and foreign cells or
response to foreign cells, such as might occur
tissues (called “non-self”). Similar types of
with an organ transplant. These same sites
glycoproteins and glycolipids are found on the
serve as places for antibodies to attach and
surfaces of viruses and may change frequently,
either destroy or inhibit the activity of the virus.
preventing immune cells from recognizing and
Unfortunately, these recognition sites on HIV
attacking them.
change at a rapid rate because of mutations,
These carbohydrates on the exterior surface of making the production of an effective vaccine
the cell—the carbohydrate components of both against the virus very difficult, as the virus
glycoproteins and glycolipids—are collectively evolves and adapts. A person infected with HIV
referred to as the glycocalyx (meaning “sugar will quickly develop different populations, or
coating”). The glycocalyx is highly hydrophilic variants, of the virus that are distinguished by
and attracts large amounts of water to the differences in these recognition sites. This rapid
surface of the cell. This aids in the interaction of change of surface markers decreases the
the cell with its watery environment and in the effectiveness of the person’s immune system in
cell’s ability to obtain substances dissolved in attacking the virus, because the antibodies will
the water. As discussed above, the glycocalyx is not recognize the new variations of the surface
also important for cell identification, self/non- patterns. In the case of HIV, the problem is
self determination, and embryonic compounded by the fact that the virus
development, and is used in cell-cell specifically infects and destroys cells involved in
attachments to form tissues. the immune response, further incapacitating
the host.

How Viruses Infect Specific Organs

Glycoprotein and glycolipid patterns on the

surfaces of cells give many viruses an
opportunity for infection. HIV and hepatitis
viruses infect only specific organs or cells in the
human body. HIV is able to penetrate the
plasma membranes of a subtype of
lymphocytes called T-helper cells, as well as
 are no double bonds between adjacent carbon
atoms. This results in tails that are relatively
straight. In contrast, unsaturated fatty acids do
not contain a maximal number of hydrogen
atoms, but they do contain some double bonds
between adjacent carbon atoms; a double bond
results in a bend in the string of carbons of
approximately 30 degrees (Figure 8.3).

Thus, if saturated fatty acids, with their straight

tails, are compressed by decreasing
temperatures, they press in on each other,
making a dense and fairly rigid membrane. If
unsaturated fatty acids are compressed, the
“kinks” in their tails elbow adjacent
Figu phospholipid molecules away, maintaining some
re 8.6 HIV binds to the CD4 receptor, a space between the phospholipid molecules.
glycoprotein on the surfaces of T cells. (Credit: This “elbow room” helps to maintain fluidity in
modification of work by NIH, NIAID) the membrane at temperatures at which
membranes with saturated fatty acid tails in
8.1.2 Membrane Fluidity their phospholipids would “freeze” or solidify.
The mosaic characteristic of the membrane, The relative fluidity of the membrane is
described in the fluid mosaic model, helps to particularly important in a cold environment. A
illustrate its nature. The integral proteins and cold environment tends to compress
lipids exist in the membrane as separate but membranes composed largely of saturated fatty
loosely attached molecules. These resemble the acids, making them less fluid and more
separate, multicolored tiles of a mosaic picture, susceptible to rupturing. Many organisms (fish
and they float, moving somewhat with respect are one example) are capable of adapting to
to one another. The membrane is not like a cold environments by changing the proportion
balloon, however, that can expand and contract; of unsaturated fatty acids in their membranes in
rather, it is fairly rigid and can burst if response to the lowering of the temperature.
penetrated or if a cell takes in too much water. Animals have an additional membrane
However, because of its mosaic nature, a very constituent that assists in maintaining fluidity.
fine needle can easily penetrate a plasma Cholesterol, which lies alongside the
membrane without causing it to burst, and the phospholipids in the membrane, tends to
membrane will flow and self-seal when the dampen the effects of temperature on the
needle is extracted. membrane. Thus, this lipid functions as a buffer,
The mosaic characteristics of the membrane preventing lower temperatures from inhibiting
explain some but not all of its fluidity. There are fluidity and preventing increased temperatures
two other factors that help maintain this fluid from increasing fluidity too much. Thus,
characteristic. One factor is the nature of the cholesterol extends, in both directions, the
phospholipids themselves. In their saturated range of temperature in which the membrane is
form, the fatty acids in phospholipid tails are appropriately fluid and consequently functional.
saturated with bound hydrogen atoms. There Cholesterol also serves other functions, such as
organizing clusters of transmembrane proteins a way of obtaining these materials from
into lipid rafts. extracellular fluids. This may happen passively,
as certain materials move back and forth, or the
Table 8.1 The components and functions of the
cell may have special mechanisms that facilitate
plasma membrane.
transport. Some materials are so important to a
Component Location cell that it spends some of its energy,
hydrolyzing adenosine triphosphate (ATP), to
Main fabric of the obtain these materials. All cells spend the
Phospholipid
membrane majority of their energy to maintain an
imbalance of sodium and potassium ions
Attached between
between the interior and exterior of the cell.
phospholipids and
Cholesterol
between the two The most direct forms of membrane transport
phospholipid layers are passive. Passive transport is a naturally
occurring phenomenon and does not require
Embedded within the
the cell to exert any of its energy to accomplish
Integral proteins phospholipid layer(s).
the movement. In passive transport, substances
(for example, May or may not
move from an area of higher concentration to
integrins) penetrate through
an area of lower concentration. A physical space
both layers
in which there is a range of concentrations of a
On the inner or outer single substance is said to have a concentration
surface of the gradient.
Peripheral
phospholipid bilayer;
proteins 8.2.1 Selective Permeability
not embedded within
the phospholipids Plasma membranes are asymmetric: the interior
of the membrane is not identical to the exterior
Carbohydrates Generally attached to
of the membrane. In fact, there is a
(components of proteins on the
considerable difference between the array of
glycoproteins outside membrane
phospholipids and proteins between the two
and glycolipids) layer
leaflets that form a membrane. On the interior
of the membrane, some proteins serve to
anchor the membrane to fibers of the
Passive Transport cytoskeleton. There are peripheral proteins on
Plasma membranes must allow certain the exterior of the membrane that bind
substances to enter and leave a cell, and elements of the extracellular matrix.
prevent some harmful materials from entering Carbohydrates,
and some essential materials from leaving. In attached to lipids or proteins, are also found on
other words, plasma membranes are selectively the exterior surface of the plasma membrane.
permeable—they allow some substances to These carbohydrate complexes help the cell
pass through, but not others. If they were to bind substances that the cell needs in the
lose this selectivity, the cell would no longer be extracellular fluid. This adds considerably to the
able to sustain itself, and it would be destroyed. selective nature of plasma membranes (Figure
Some cells require larger amounts of specific 8.7).
substances than do other cells; they must have
 high concentration to an area of low
concentration until the concentration is equal
across a space. You are familiar with diffusion of
substances through the air. For example, think
about someone opening a bottle of ammonia in
a room filled with people. The ammonia gas is
at its highest concentration in the bottle; its
Figure 8.7 The exterior surface of the plasma lowest concentration is at the edges of the
membrane is not identical to the interior room. The ammonia vapor will diffuse, or
surface of the same membrane. spread away, from the bottle, and gradually,
more and more people will smell the ammonia
Recall that plasma membranes are amphipathic: as it spreads. Materials move within the cell’s
They have hydrophilic and hydrophobic regions. cytosol by diffusion, and certain materials move
This characteristic helps the movement of some through the plasma membrane by diffusion
materials through the membrane and hinders (Figure 8.8). Diffusion expends no energy. On
the movement of others. Lipid-soluble material the contrary, concentration gradients are a form
with a low molecular weight can easily slip of potential energy, dissipated as the gradient is
through the hydrophobic lipid core of the eliminated.
membrane. Substances such as the fat- soluble
vitamins A, D, E, and K readily pass through the
plasma membranes in the digestive tract and
other tissues. Fat-soluble drugs and hormones
also gain easy entry into cells and are readily
transported into the body’s tissues and organs.
Molecules of oxygen and carbon dioxide have
no charge and so pass through membranes by Figure 8.8 Diffusion through a permeable
simple diffusion. membrane moves a substance from an area of
Polar substances present problems for the high concentration down its concentration
membrane. While some polar molecules gradient. (Credit: modification of work by
connect easily with the outside of a cell, they Mariana Ruiz Villareal)
cannot readily pass through the lipid core of the Each separate substance in a medium, such as
plasma membrane. Additionally, while small the extracellular fluid, has its own concentration
ions could easily slip through the spaces in the gradient, independent of the concentration
mosaic of the membrane, their charge prevents gradients of other materials. In addition, each
them from doing so. Ions such as sodium, substance will diffuse according to that
potassium, calcium, and chloride must have gradient. Within a system, there will be different
special means of penetrating plasma rates of diffusion of the different substances in
membranes. Larger polar molecules, such as the medium.
simple sugars and amino acids also need help
with transport across plasma membranes. Factors That Affect Diffusion

8.2.2 Diffusion Molecules move constantly in a random

manner, at a rate that depends on their mass,
Diffusion is a passive process of transport. A their environment, and the amount of thermal
single substance tends to move from an area of
energy they possess, which in turn is a function leads to unconsciousness and possibly coma
of temperature. This movement accounts for because of the decrease in diffusion rate within
the diffusion of molecules through whatever the cells.
medium in which they are localized. A
8.2.3 Facilitated diffusion
substance will tend to move into any space
available to it until it is evenly distributed In facilitated diffusion, materials diffuse across
throughout it. After a substance has diffused the plasma membrane with the help of
completely through a space, removing its membrane proteins. A concentration gradient
concentration gradient, molecules will still move exists that would allow these materials to
around in the space, but there will be no net diffuse into the cell without expending cellular
movement of the number of molecules from energy. However, these materials are ions or
one area to another. This lack of a concentration polar molecules that are repelled by the
gradient in which there is no net movement of a hydrophobic parts of the cell membrane.
substance is known as dynamicequilibrium. Facilitated diffusion proteins shield these
While diffusion will go forward in the presence materials from the repulsive force of the
of a concentration gradient of a substance, membrane, allowing them to diffuse into the
several factors affect the rate of diffusion. cell. These proteins are called transportproteins
and can be channels or carrier proteins.
“Steepness” of the concentration gradient: The
greater the difference in concentration, the Channels
more rapid the diffusion. The closer the
distribution of the material gets to equilibrium, Channelproteins are transmembrane proteins
the slower the rate of diffusion becomes. that fold in such as way as to form a channel or
pore through the membrane. Each channel is
Mass of the molecules diffusing: Heavier specific for one particular substance. Channel
molecules move more slowly; therefore, they proteins have hydrophilic domains exposed to
diffuse more slowly. the intracellular and extracellular fluids. In
addition, they have a hydrophilic channel
Temperature: Higher temperatures increase the
through their core that provides a hydrated
energy and therefore the movement of the
opening through the membrane layers
molecules, increasing the rate of diffusion.
(Figure8.9). Passage through the channel allows
Solvent density: As the density of a solvent polar compounds to avoid the nonpolar central
increases, the rate of diffusion decreases. The layer of the plasma membrane that would
molecules slow down because they have a more otherwise slow or prevent their entry into the
difficult time getting through the denser cell. Aquaporins are channel proteins that allow
medium. If the medium is less dense, diffusion water to pass through the membrane at a very
increases. Because cells primarily use diffusion high rate.
to move materials within the cytoplasm, any
increase in the cytoplasm’s density will inhibit
the movement of the materials. An example of
this is a person experiencing dehydration. As the
body’s cells lose water, the rate of diffusion
decreases in the cytoplasm, and the cells’
functions deteriorate. Neurons tend to be very
sensitive to this effect. Dehydration frequently
 Figure 8.10 Some substances are able to move
down their concentration gradient across the
plasma membrane with the aid of carrier
proteins. Carrier proteins change shape as they
move molecules across the membrane. (Credit:
modification of work by Mariana Ruiz Villareal)

There are a finite number of each type of carrier

Figure 8.9 Facilitated transport moves proteins in any membrane. This can cause
substances down their concentration gradients. problems in transporting enough of the material
They may cross the plasma membrane with the for the cell to function properly. When all of the
aid of channel proteins. (Credit: modification of proteins are bound to their ligands, they are
work by Mariana Ruiz Villareal) saturated and the rate of transport is at its
Some channel proteins are always open but maximum. Increasing the concentration
many are “gated,” meaning that they can be gradient at this point will not result in an
opened and closed. If a channel is ligand-gated, increased rate of transport.
the attachment of a particular molecule to the An example of this process occurs in the kidney.
channel protein may cause it to open. Other Glucose, water, salts, ions, and amino acids
channels are voltage-gated, requiring a change needed by the body are filtered out of the blood
in voltage across the membrane to open them. in one part of the kidney. This filtrate, which
Cells involved in the transmission of electrical includes glucose, is then reabsorbed in another
impulses, such as nerve and muscle cells, have part of the kidney. Because there are only a
voltage-gated ion channels in their membranes. finite number of carrier proteins for glucose, if
Carrier Proteins more glucose is present than the proteins can
handle, the excess is not transported and it is
Another type of transmembrane transporter excreted from the body in the urine. In a
protein is a carrierprotein. Like channels, carrier diabetic individual, this is described as “spilling
proteins are usually specific for particular glucose into the urine.”
molecules. A carrier proteins binds a substance
and, in doing so, triggers a change of its own A different group of carrier proteins called
shape, moving the bound molecule across the glucose transport proteins, or GLUTs, are
membrane (Figure8.10). Carrier proteins are involved in transporting glucose and other
used to transport molecules that are too large hexose sugars into cells within the body. The
to pass through channels, such as amino acids hormone insulin, increases the number of
and glucose. GLUTs on cells, causing them to take glucose
from the blood when its levels are high. It is this
process that is compromised in diabetic
individuals.

Channel proteins transport much more quickly

than do carrier proteins. Channel proteins
facilitate diffusion at a rate of tens of millions of
molecules/second, whereas carrier proteins
work at a rate of a thousand to a million
molecules/second.

8.2.4 Osmosis
Figure 8.11 In osmosis, water always moves
Osmosis is the diffusion of water across a
from an area of higher water concentration to
semipermeable membrane. Since it is diffusion,
one of lower concentration. In the diagram
it depends on the concentration gradient, or the
shown, the solute cannot pass through the
amount of water on each side of the
selectively permeable membrane, but the water
membrane. The amount of water in a solute is
can.
inversely proportional to the concentration of
solutes. In other words, the higher the To illustrate this, imagine two full glasses of
concentration of water, the lower the water. One has a single teaspoon of sugar in it,
concentration of solutes, and vice versa. Water whereas the second one contains one-quarter
can move readily across most membranes, due cup of sugar. If the total volume of the solutions
in part to the presence of aquaporins; however, in both cups is the same, which cup contains
the membrane limits the diffusion of solutes in more water? Because the large amount of sugar
the water. in the second cup takes up much more space
than the teaspoon of sugar in the first cup, the
Mechanism of Osmosis
first cup has more water in it.
Osmosis is a special case of diffusion. Water, like
Returning to the beaker example, recall that it
other substances, moves from an area of high
has a mixture of solutes on either side of the
concentration to one of low concentration. An
membrane. A principle of diffusion is that the
obvious question is what makes water move at
molecules move around and will spread evenly
all? Imagine a beaker with a semipermeable
throughout the medium if they can. However,
membrane separating the two sides or halves
only the material capable of getting through the
(Figure8.11). On both sides of the membrane
membrane will diffuse through it. In this
the water level is the same, but there are
example, the solute cannot diffuse through the
different concentrations of a dissolved
membrane, but the water can. Water has a
substance, or solute, that cannot cross the
concentration gradient in this system. Thus,
membrane (otherwise the concentrations on
water will diffuse down its concentration
each side would be balanced by the solute
gradient, crossing the membrane to the side
crossing the membrane). If the volume of the
where it is less concentrated. This diffusion of
solution on both sides of the membrane is the
water through the membrane—osmosis—will
same, but the concentrations of solute are
continue until the concentration gradient of
different, then there are different amounts of
water goes to zero or until the hydrostatic
water, the solvent, on either side of the
pressure of the water balances the osmotic
membrane.
pressure. Osmosis proceeds constantly in living
systems.

8.2.5 Tonicity

Tonicity describes how an extracellular solution

can change the volume of a cell by affecting
osmosis. A solution’s tonicity often directly
correlates with the osmolarity of the solution.
Osmolarity describes the total solute Figure 8.12 Osmotic pressure changes the
concentration of the solution. A solution with shape of red blood cells in hypertonic, isotonic,
low osmolarity has a greater number of water and hypotonic solutions. (Credit: Mariana Ruiz
molecules relative to the number of solute Villareal)
particles; a solution with high osmolarity has
fewer water molecules with respect to solute Hypotonic Solutions
particles. In a situation in which solutions of two
In a hypotonic situation, the extracellular fluid
different osmolarities are separated by a
has lower osmolarity than the fluid inside the
membrane permeable to water, though not to
cell. The extracellular fluid has a higher
the solute, water will move from the side of the
concentration of water than does the cell and
membrane with lower osmolarity (and more
water will move down its concentration gradient
water) to the side with higher osmolarity (and
and enter the cell.
less water). This effect makes sense if you
remember that the solute cannot move across Hypertonic Solutions
the membrane, and thus the only component in
In a hypertonic solution (hyper- = “more”), the
the system that can move—the water—moves
extracellular fluid has a higher osmolarity than
along its own concentration gradient.
the cell’s cytoplasm. The fluid contains less
Three terms—hypotonic, isotonic, and water than the cell does, so water will leave the
hypertonic—are used to relate the osmolarity of cell.
a cell to the osmolarity of the extracellular fluid.
Isotonic Solutions
In living systems, the point of reference is
always the cytoplasm, so the prefix hypo- In an isotonic solution, the extracellular fluid
(“lower”) means that the extracellular fluid has has the same osmolarity as the cell. There is no
a lower concentration of solutes, or a lower net movement of water into or out of the cell
osmolarity, than the cell cytoplasm. Blood cells (although water will still move in and out).
and plant cells in hypertonic, isotonic, and
Concept Check
hypotonic solutions take on characteristic
appearances (Figure 8.12). A doctor injects a patient with what the doctor
thinks is an isotonic saline solution. The patient
dies, and an autopsy reveals that many red
blood cells have been destroyed. Do you think
the solution the doctor injected was really
isotonic?

8.2.6 Tonicity in Living Systems

A red blood cell will burst, or lyse, when it swells
beyond the plasma membrane’s capability to
expand. In contrast, when excessive amounts of
water leave a red blood cell, the cell shrinks, or
crenates. Crenation has the effect of
concentrating the solutes left in the cell, making
the cytosol denser and interfering with diffusion
within the cell. The cell’s ability to function will Figure 8.14 Without adequate water, the plant
be compromised and it may die. (Figure 8.12). on the left has lost turgor pressure, visible in its
wilting; the turgor pressure is restored by
Living things have ways of controlling the effects watering it (right). (Credit: Victor M. Vicente
of osmosis—a mechanism called Selvas)
osmoregulation. Some organisms, such as
plants, fungi, bacteria, and some protists, have Tonicity is a concern for all living things. For
cell walls that surround the plasma membrane example, paramecia and amoebas, which are
and prevent cells from lysing. In fact, the protists that lack cell walls, have contractile
cytoplasm in plants is always slightly hypertonic vacuoles. This vesicle collects excess water from
to the cellular environment, and water will the cell and pumps it out, keeping the cell from
always enter a cell if water is available. This lysing as it takes on water from its environment
inflow of water produces turgor pressure, which (Figure 8.15).
stiffens the cell walls of the plant (Figure 8.13).
In nonwoody plants, turgor pressure supports
the plant. If the plant is not watered, the
extracellular fluid will become hypertonic,
causing water to leave the cell. In this condition,
the cell membrane detaches from the cell wall
and constricts the cytoplasm. This process,
called plasmolysis, causes plants to lose turgor
pressure (Figure 8.14).
Figure 8.15 A paramecium’s contractile vacuole,
here visualized using bright field light
microscopy at 480x magnification, continuously
pumps water out of the organism’s body to keep
it from bursting in a hypotonic medium. (Credit:
modification of work by NIH; scale-bar data
from Matt Russell)

Many marine invertebrates have internal salt

Figure 8.13 The turgor pressure within a plant levels matched to their environments, making
cell depends on the tonicity of the solution that them isotonic with the water in which they live.
it is bathed in. (Credit: modification of work by Fish, however, must spend approximately five
Mariana Ruiz Villareal) percent of their metabolic energy maintaining
osmotic homeostasis. Freshwater fish live in an
environment that is hypotonic to their cells.
These fish actively take in salt through their gills
and excrete diluted urine to rid themselves of Because ions move into and out of cells and
excess water. Saltwater fish live in the reverse because cells contain proteins that do not move
environment, which is hypertonic to their cells, across the membrane and are mostly negatively
and they secrete salt through their gills and charged, there is also an electrical gradient, a
excrete highly concentrated urine. difference of charge, across the plasma
membrane.
In vertebrates, the kidneys regulate the amount
of water in the body. Osmoreceptors are The interior of living cells is electrically negative
specialized cells in the brain that monitor the with respect to the extracellular fluid
concentration of solutes in the blood. If the surrounding them. At the same time, cells have
levels of solutes increase beyond a certain a lower concentration of (Na+) than does the
range, a hormone is released that retards water extracellular fluid. Therefore, both the
loss through the kidney and dilutes the blood to concentration
safer levels. Animals also have high
gradient and the electrical gradient tend to
concentrations of albumin, which is produced
drive Na+ into the cell. Conversely, cells have a
by the liver, in their blood. This protein is too
higher concentration of K+ than the
large to pass easily through plasma membranes
extracellular fluid does. Therefore, the
and is a major factor in controlling the osmotic
concentration gradient tends to drive K+ out of
pressures applied to tissues.
the cell, while the electrical gradient tends to
8.3 | Active Transport drive it inside the cell. The combined gradient of
concentration and electrical charge that affects
By the end of this section, you will be able
an ion is called its electrochemical
to:Understand how electrochemical gradients
gradient (Figure 8.16).
affect ionsDistinguish between primary active
transport and secondary active transport

Active transport mechanisms require the use of

the cell’s energy, usually in the form of
adenosine triphosphate (ATP). If a substance
must move into the cell against its
concentration gradient—that is, if the
concentration of the substance inside the cell is
greater than its concentration in the
extracellular fluid (and vice versa)—the cell
must use energy to move the substance. Some
active transport mechanisms move small-
molecular weight materials, such as ions, Figure 8.16 Electrochemical gradients arise from
through the membrane. Other mechanisms the combined effects of concentration gradients
transport much larger molecules. and electrical gradients. (Credit:
“Synaptitude”/Wikimedia Commons)
8.3.1 Electrochemical Gradient
Concept Check
We have discussed simple concentration
gradients—different concentrations of a
substance across a space or a membrane—but
in living systems, gradients are more complex.
Injection of a potassium solution into a person’s Two mechanisms exist for the transport of
blood is lethal; this is used in capital small-molecular weight material and small
punishment and euthanasia. Why do you think molecules. Primary active transport is directly
a potassium solution injection is lethal? dependent on ATP. Secondary active transport
does not directly require ATP, because it uses
Moving Against a Gradient
electrochemical gradients established by
To move substances against a concentration or primary active transport for fuel. Primary active
electrochemical gradient, the cell must use transport must occur first to in order to allow
energy, usually in the form of ATP. Active secondary active transport to occur. Although it
transport proteins, called pumps, work against does not use ATP, secondary active transport is
electrochemical gradients. Small substances still considered active because it requires
constantly pass through plasma membranes. energy.
Active transport maintains concentrations of
8.3.2 Primary Active Transport
ions and other substances needed by living cells
in the face of these passive movements. Much One of the most important pumps in animals
of a cell’s supply of metabolic energy may be cells is the sodium-potassium pump (Na+-K+
spent maintaining these processes. ATPase), which maintains the electrochemical
gradient and the correct concentrations of Na+
Proteins for Active Transport
and K+ in living cells. The sodium-potassium
The specific proteins that facilitate active pump moves two K+ into the cell while moving
transport are called transporters. There are three Na+ out of the cell (Figure 8.18).
three types of transporters (Figure 8.17). A
uniporter carries one specific ion or molecule. A
symporter carries two different ions or
molecules, both in the same direction. An
antiporter carries two different ions or
molecules in different directions. All of these
transporters can transport small, uncharged
organic molecules such as glucose.

Figure 8.18 Primary active transport moves ions

across a membrane, creating an electrochemical
gradient (electrogenic transport). (Credit:
[Link] staff. “Blausen gallery 2014”.
Wikiversity Journal of Medicine.)

The sodium-potassium pump works in the

Figure 8.17 A uniporter carries one molecule or following six steps:
ion. A symporter carries two different molecules 1.
or ions, both in the same direction. An
antiporter also carries two different molecules 1. Three sodium ions bind to the
or ions, but in different directions. (credit: protein.
modification of work by “Lupask”/Wikimedia
Commons)
 2. ATP is hydrolyzed by the protein across the membrane. ATP performs cellular
carrier and a low-energy work using this basic form of energy coupling
phosphate group attaches to it. through phosphorylation. Here, the exergonic
(energy-releasing) process of ATP breakdown
3. The carrier changes shape and
“pays for” the endergonic (energy-requiring)
opens towards the exterior of
process of moving ions against their
the membrane. The three
concentration gradients.
sodium ions are released.

4. Two potassium ions attach to

the protein, causing the low-
energy phosphate group to
detach.

5. The carrier protein changes

shape so that is open towards
the interior of the cell.

6. The two potassium ions are

released into the cytoplasm and
the process begins again.

Several things have happened as a result of this Figure 8.19 The sodium-potassium pump is an
process. First, there are now more sodium ions example of energy coupling. The energy derived
outside of the cell than inside and more from exergonic ATP hydrolysis is used to pump
potassium ions inside than out. Second, since sodium and potassium ions across the cell
three sodium ions moved out for each two membrane.
potassium ions that moved in, the interior is 8.3.3 Secondary Active Transport (Co-
slightly more negative relative to the exterior. transport)
This difference in charge is important in creating
the conditions necessary for secondary active Secondary active transport moves a solute
transport. The sodium-potassium pump is, against its concentration gradient, an
therefore, an electrogenic pump (a pump that endergonic process, by moving another solute
creates a charge imbalance), creating an down its concentration gradient, an exergonic
electrical imbalance across the membrane and process. For instance, as sodium ion
contributing to the membrane potential. concentrations build outside of the plasma
membrane because of the action of the sodium-
The sodium-potassium pump (Na+/K+ pump) is potassium pump, an electrochemical gradient is
one example of energy coupling. Each cycle of created. If a channel protein exists and is open,
the Na+/K+ pump moves three sodium out of the sodium ions will be pulled through the
the cell and brings two potassium into the cell. membrane, down their concentration gradient.
For each cycle, one ATP is hydrolyzed and its This exergonic movement is used to transport
free phosphate group is transferred to the other substances that can attach themselves to
pump protein. This process of a phosphate the transport protein through the membrane
group binding to a molecule is called (Figure 8.20). Many amino acids, as well as
phosphorylation. Phosphorylation of the pump glucose, enter a cell this way.
protein causes it to change shape, moving ions
 pinocytosis, and receptor-mediated
endocytosis.

Phagocytosis

Phagocytosis (“cell eating”) is the process by

which large particles, such as other cells or
relatively large particles, are taken in by a cell.
For example, when microorganisms invade the
human body, a type of white blood cell called a
neutrophil will “eat” the invaders through
Figure 8.20 An electrochemical gradient, phagocytosis, surrounding and engulfing the
created by primary active transport, can move microorganism, which is then destroyed by
other substances against their concentration lysosomes inside the neutrophil (Figure 8.21).
gradients, a process called co-transport or
secondary active transport. (Credit:
modification of work by Mariana Ruiz Villareal)

Bulk Transport

n addition to moving small ions and molecules

through the membrane, cells also need to
remove and take in larger molecules and
particles (see Table 8.2 for examples). Some
cells are even capable of engulfing entire
unicellular microorganisms. You might have
correctly hypothesized that the uptake and
release of large particles by the cell requires
energy. A large particle, however, cannot pass
through the membrane, even with energy
supplied by the cell.

8.4.1 Endocytosis

Endocytosis is a type of active transport that

moves particles, such as large molecules, parts
of cells, and even whole cells, into a cell. There Figure 8.21 In phagocytosis, the cell membrane
are different variations of endocytosis, but all surrounds the particle and engulfs it. (Credit:
share a common characteristic: The plasma Mariana Ruiz Villareal)
membrane of the cell invaginates, forming a In preparation for phagocytosis, a portion of the
pocket around the target particle. The pocket inward-facing surface of the plasma membrane
pinches off, resulting in the particle being becomes coated with a protein called clathrin,
contained in a newly created intracellular which stabilizes this section of the membrane.
vesicle formed from the plasma membrane. The The coated portion of the membrane then
three types of endocytosis are phagocytosis, extends from the body of the cell and surrounds
the particle, eventually enclosing it. Once the
vesicle containing the particle is enclosed within specific binding affinity for certain substances
the cell, the clathrin disengages from the (Figure 8.23).
membrane and the vesicle merges with a
Receptor-mediated endocytosis, as in
lysosome for the breakdown of the material in
phagocytosis, uses clathrin protein attached to
the newly formed compartment. When
the cytoplasmic side of the plasma membrane.
accessible nutrients from the degradation of the
Some human diseases are caused by the failure
vesicular contents have been extracted, the
of receptor-mediated endocytosis. For example,
newly formed endosome merges with the
the form of cholesterol termed low-density
plasma membrane and releases its contents into
lipoprotein or LDL (also referred to as “bad”
the extracellular fluid. The endosomal
cholesterol) is removed from the blood by
membrane again becomes part of the plasma
receptor-mediated endocytosis. In the human
membrane.
genetic disease familial hypercholesterolemia,
Pinocytosis the LDL receptors are defective or missing
entirely. People with this condition have life-
Through pinocytosis (“cell drinking”), cells take
threatening levels of cholesterol in their blood,
in molecules, including water, which the cell
because their cells cannot clear LDL particles
needs from the extracellular fluid. Pinocytosis
from their blood.
results in a much smaller vesicle than does
phagocytosis, and the vesicle does not need to Although receptor-mediated endocytosis is
merge with a lysosome (Figure 8.22). designed to bring specific substances that are
normally found in the extracellular fluid into the
cell, other substances may gain entry into the
cell at the same site. Flu viruses, diphtheria, and
cholera toxin all have sites that cross-react with
normal receptor-binding sites and gain entry
into cells.

Figure 8.22 In pinocytosis, the cell membrane

invaginates, surrounds a small volume of fluid,
and pinches off. (Credit: Mariana Ruiz Villareal)

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is a targeted Figure

variation of endocytosis that employs receptor 8.23 In receptor-mediated endocytosis, uptake
proteins in the plasma membrane that have a of substances by the cell is targeted to a single
type of substance that binds to the receptor on Active/ Material
Transport Method
the external surface of the cell membrane. Passive Transported
(Credit: modification of work by Mariana Ruiz
Villareal) Small-molecular
Diffusion Passive
weight material
8.4.2 Exocytosis
Osmosis Passive Water
The reverse process of moving material into a
cell is the process of exocytosis. The purpose of Facilitated Sodium, potassium,
Passive
exocytosis is to expel material from the cell into transport/diffusion calcium, glucose
the extracellular fluid. Waste material is
Primary active Sodium, potassium,
enveloped in vesicle, which fuses with the Active
transport calcium
interior of the plasma membrane, expelling the
waste material into the extracellular space Secondary active Amino acids,
Active
(Figure 8.24). Cells also use exocytosis to transport lactose
secrete proteins such as hormones,
Large
neurotransmitters, or parts of the extracellular
macromolecules,
matrix. Phagocytosis Active
whole cells, or
cellular structures

Pinocytosis and Small molecules

Active
potocytosis (liquids/water)

Receptor-mediated Large quantities of

Active
endocytosis macromolecules

Fig
ure 8.24 In exocytosis, vesicles containing
substances fuse with the plasma membrane.
The contents are then released to the exterior
of the cell. (Credit: modification of work by
Mariana Ruiz Villareal)

Table 8.2 Methods of transport, energy

requirements, and types of material The Action Potential
transported
The functions of the nervous system—
sensation, integration, and response—depend
on the functions of the neurons underlying
these pathways. To understand how neurons
are able to communicate, it is necessary to
describe the role of an excitable membrane in
generating these signals. The basis of this
communication is the action potential, which
demonstrates how changes in the membrane Figure 1. Cell Membrane and Transmembrane
can constitute a signal. Looking at the way these Proteins The cell membrane is composed of a
signals work in more variable circumstances phospholipid bilayer and has many
involves a look at graded potentials, which will transmembrane proteins, including different
be covered in the next section. types of channel proteins that serve as ion
channels.
Electrically Active Cell Membranes
The sodium/potassium pump requires energy in
Most cells in the body make use of charged the form of adenosine triphosphate (ATP), so it
particles, ions, to build up a charge across the is also referred to as an ATPase. As was
cell membrane. Previously, this was shown to be explained in the cell chapter, the concentration
a part of how muscle cells work. For skeletal of Na+ is higher outside the cell than inside, and
muscles to contract, based on excitation– the concentration of K+ is higher inside the cell
contraction coupling, requires input from a is higher than outside. That means that this
neuron. Both of the cells make use of the cell pump is moving the ions against the
membrane to regulate ion movement between concentration gradients for sodium and
the extracellular fluid and cytosol. potassium, which is why it requires energy. In
fact, the pump basically maintains those
As you learned in the chapter on cells, the cell
concentration gradients.
membrane is primarily responsible for
regulating what can cross the membrane and Ion channels are pores that allow specific
what stays on only one side. The cell membrane charged particles to cross the membrane in
is a phospholipid bilayer, so only substances response to an existing concentration gradient.
that can pass directly through the hydrophobic Proteins are capable of spanning the cell
core can diffuse through unaided. Charged membrane, including its hydrophobic core, and
particles, which are hydrophilic by definition, can interact with the charge of ions because of
cannot pass through the cell membrane without the varied properties of amino acids found
assistance (Figure 1). Transmembrane proteins, within specific domains or regions of the
specifically channel proteins, make this possible. protein channel. Hydrophobic amino acids are
Several channels, as well as specialized energy found in the domains that are apposed to the
dependent “ion-pumps,” are necessary to hydrocarbon tails of the phospholipids.
generate a transmembrane potential and to Hydrophilic amino acids are exposed to the fluid
generate an action potential. Of special interest environments of the extracellular fluid and
is the carrier protein referred to as the cytosol. Additionally, the ions will interact with
sodium/potassium pump that moves sodium the hydrophilic amino acids, which will be
ions (Na+) out of a cell and potassium ions (K+) selective for the charge of the ion. Channels for
into a cell, thus regulating ion concentration on cations (positive ions) will have negatively
both sides of the cell membrane.
charged side chains in the pore. Channels for
anions (negative ions) will have positively
charged side chains in the pore. This is
called electrochemical exclusion, meaning that
the channel pore is charge-specific.

Ions can also be specified by the diameter of the

pore. The distance between the amino acids will
be specific for the diameter of the ion when it
dissociates from the water molecules Figure 2. Ligand-Gated Channels When the
surrounding it. Because of the surrounding ligand, in this case the neurotransmitter
water molecules, larger pores are not ideal for acetylcholine, binds to a specific location on the
smaller ions because the water molecules will extracellular surface of the channel protein, the
interact, by hydrogen bonds, more readily than pore opens to allow select ions through. The
the amino acid side chains. This is called size ions, in this case, are cations of sodium, calcium,
exclusion. Some ion channels are selective for and potassium.
charge but not necessarily for size, and thus are A mechanically gated channel opens because of
called a nonspecific channel. These nonspecific a physical distortion of the cell membrane.
channels allow cations—particularly Na+, K+, and Many channels associated with the sense of
Ca2+—to cross the membrane, but exclude touch (somatosensation) are mechanically
anions. gated. For example, as pressure is applied to the
Ion channels do not always freely allow ions to skin, these channels open and allow ions to
diffuse across the membrane. They are opened enter the cell. Similar to this type of channel
by certain events, meaning the channels would be the channel that opens on the basis of
are gated. So another way that channels can be temperature changes, as in testing the water in
categorized is on the basis of how they are the shower (Figure 3).
gated. Although these classes of ion channels
are found primarily in cells of nervous or
muscular tissue, they also can be found in cells
of epithelial and connective tissues.

A ligand-gated channel opens because a

signaling molecule, a ligand, binds to the
extracellular region of the channel. This type of
channel is also known as an ionotropic
receptor because when the ligand, known as a Figure 3. Mechanically Gated Channels When a
neurotransmitter in the nervous system, binds mechanical change occurs in the surrounding
to the protein, ions cross the membrane tissue, such as pressure or touch, the channel is
changing its charge (Figure 2). physically opened. Thermoreceptors work on a
similar principle. When the local tissue
temperature changes, the protein reacts by
physically opening the channel.

A voltage-gated channel is a channel that

responds to changes in the electrical properties
of the membrane in which it is embedded. The electrical state of the cell membrane can
Normally, the inner portion of the membrane is have several variations. These are all variations
at a negative voltage. When that voltage in the membrane potential. A potential is a
becomes less negative, the channel begins to distribution of charge across the cell membrane,
allow ions to cross the membrane (Figure 4). measured in millivolts (mV). The standard is to
compare the inside of the cell relative to the
outside, so the membrane potential is a value
representing the charge on the intracellular side
of the membrane based on the outside being
zero, relatively speaking (Figure 6).

Figure 4. Voltage-Gated Channels Voltage-gated

channels open when the transmembrane
voltage changes around them. Amino acids in
the structure of the protein are sensitive to
charge and cause the pore to open to the
selected ion. Figure 6. Measuring Charge across a
Membrane with a Voltmeter A recording
A leakage channel is randomly gated, meaning electrode is inserted into the cell and a
that it opens and closes at random, hence the reference electrode is outside the cell. By
reference to leaking. There is no actual event comparing the charge measured by these two
that opens the channel; instead, it has an electrodes, the transmembrane voltage is
intrinsic rate of switching between the open and determined. It is conventional to express that
closed states. Leakage channels contribute to value for the cytosol relative to the outside.
the resting transmembrane voltage of the
excitable membrane (Figure 5). The concentration of ions in extracellular and
intracellular fluids is largely balanced, with a net
neutral charge. However, a slight difference in
charge occurs right at the membrane surface,
both internally and externally. It is the
difference in this very limited region that has all
the power in neurons (and muscle cells) to
generate electrical signals, including action
potentials.
Figure 5. Leakage Channels In certain situations, Before these electrical signals can be described,
ions need to move across the membrane the resting state of the membrane must be
randomly. The particular electrical properties of explained. When the cell is at rest, and the ion
certain cells are modified by the presence of channels are closed (except for leakage
this type of channel. channels which randomly open), ions are
distributed across the membrane in a very
The Membrane Potential
predictable way. The concentration of
Na+ outside the cell is 10 times greater than the
concentration inside. Also, the concentration of membrane at a voltage of −70 mV, so the
K+ inside the cell is greater than outside. The sodium cation entering the cell will cause it to
cytosol contains a high concentration of anions, become less negative. This is known
in the form of phosphate ions and negatively as depolarization, meaning the membrane
charged proteins. Large anions are a component potential moves toward zero.
of the inner cell membrane, including
The concentration gradient for Na+ is so strong
specialized phospholipids and proteins
that it will continue to enter the cell even after
associated with the inner leaflet of the
the membrane potential has become zero, so
membrane (leaflet is a term used for one side of
that the voltage immediately around the pore
the lipid bilayer membrane). The negative
begins to become positive. The electrical
charge is localized in the large anions.
gradient also plays a role, as negative proteins
With the ions distributed across the membrane below the membrane attract the sodium ion.
at these concentrations, the difference in charge The membrane potential will reach +30 mV by
is measured at −70 mV, the value described as the time sodium has entered the cell.
the resting membrane potential. The exact
As the membrane potential reaches +30 mV,
value measured for the resting membrane
other voltage-gated channels are opening in the
potential varies between cells, but −70 mV is
membrane. These channels are specific for the
most commonly used as this value. This voltage
potassium ion. A concentration gradient acts on
would actually be much lower except for the
K+, as well. As K+ starts to leave the cell, taking a
contributions of some important proteins in the
positive charge with it, the membrane potential
membrane. Leakage channels allow Na+ to
begins to move back toward its resting voltage.
slowly move into the cell or K+ to slowly move
This is called repolarization, meaning that the
out, and the Na+/K+ pump restores them. This
membrane voltage moves back toward the
may appear to be a waste of energy, but each
−70 mV value of the resting membrane
has a role in maintaining the membrane
potential.
potential.
Repolarization returns the membrane potential
The Action Potential
to the −70 mV value that indicates the resting
Resting membrane potential describes the potential, but it actually overshoots that value.
steady state of the cell, which is a dynamic Potassium ions reach equilibrium when the
process that is balanced by ion leakage and ion membrane voltage is below −70 mV, so a period
pumping. Without any outside influence, it will of hyperpolarization occurs while the
not change. To get an electrical signal started, K+ channels are open. Those K+ channels are
the membrane potential has to change. slightly delayed in closing, accounting for this
short overshoot.
This starts with a channel opening for Na+ in the
membrane. Because the concentration of Na+ is
higher outside the cell than inside the cell by a
factor of 10, ions will rush into the cell that are
driven largely by the concentration gradient.
Because sodium is a positively charged ion, it
will change the relative voltage immediately
inside the cell relative to immediately outside.
The resting potential is the state of the
 What is the difference between the driving
force for Na+ and K+? And what is similar about
the movement of these two ions?

The question is, now, what initiates the action

potential? The description above conveniently
glosses over that point. But it is vital to
understanding what is happening. The
membrane potential will stay at the resting
voltage until something changes. The
description above just says that a Na+ channel
Figure 7. Graph of Action Potential Plotting
opens. Now, to say “a channel opens” does not
voltage measured across the cell membrane
mean that one individual transmembrane
against time, the action potential begins with
protein changes. Instead, it means that one kind
depolarization, followed by repolarization,
of channel opens. There are a few different
which goes past the resting potential into
types of channels that allow Na+ to cross the
hyperpolarization, and finally the membrane
membrane. A ligand-gated Na+ channel will
returns to rest.
open when a neurotransmitter binds to it and a
What has been described here is the action mechanically gated Na+ channel will open when
potential, which is presented as a graph of a physical stimulus affects a sensory receptor
voltage over time in Figure 7. It is the electrical (like pressure applied to the skin compresses a
signal that nervous tissue generates for touch receptor). Whether it is a
communication. The change in the membrane neurotransmitter binding to its receptor protein
voltage from −70 mV at rest to +30 mV at the or a sensory stimulus activating a sensory
end of depolarization is a 100-mV change. That receptor cell, some stimulus gets the process
can also be written as a 0.1-V change. started. Sodium starts to enter the cell and the
membrane becomes less negative.
To put that value in perspective, think about a
battery. An AA battery that you might find in a A third type of channel that is an important part
television remote has a voltage of 1.5 V, or a 9-V of depolarization in the action potential is the
battery (the rectangular battery with two posts voltage-gated Na+ channel. The channels that
on one end) is, obviously, 9 V. The change seen start depolarizing the membrane because of a
in the action potential is one or two orders of stimulus help the cell to depolarize from
magnitude less than the charge in these −70 mV to −55 mV. Once the membrane
batteries. In fact, the membrane potential can reaches that voltage, the voltage-gated
be described as a battery. A charge is stored Na+ channels open. This is what is known as the
across the membrane that can be released threshold. Any depolarization that does not
under the correct conditions. A battery in your change the membrane potential to −55 mV or
remote has stored a charge that is “released” higher will not reach threshold and thus will not
when you push a button. result in an action potential. Also, any stimulus
that depolarizes the membrane to −55 mV or
What happens across the membrane of an beyond will cause a large number of channels to
electrically active cell is a dynamic process that open and an action potential will be initiated.
is hard to visualize with static images or through
text descriptions. View this animation to learn Because of the threshold, the action potential
more about this process. can be likened to a digital event—it either
happens or it does not. If the threshold is not After that, the inactivation gate re-opens,
reached, then no action potential occurs. If making the channel ready to start the whole
depolarization reaches −55 mV, then the action process over again.
potential continues and runs all the way to
The voltage-gated K+ channel has only one gate,
+30 mV, at which K+ causes repolarization,
which is sensitive to a membrane voltage of
including the hyperpolarizing overshoot. Also,
−50 mV. However, it does not open as quickly as
those changes are the same for every action
the voltage-gated Na+ channel does. It might
potential, which means that once the threshold
take a fraction of a millisecond for the channel
is reached, the exact same thing happens. A
to open once that voltage has been reached.
stronger stimulus, which might depolarize the
The timing of this coincides exactly with when
membrane well past threshold, will not make a
the Na+ flow peaks, so voltage-gated K+ channels
“bigger” action potential. Action potentials are
open just as the voltage-gated Na+ channels are
“all or none.” Either the membrane reaches the
being inactivated. As the membrane potential
threshold and everything occurs as described
repolarizes and the voltage passes −50 mV
above, or the membrane does not reach the
again, the channel closes—again, with a little
threshold and nothing else happens. All action
delay. Potassium continues to leave the cell for a
potentials peak at the same voltage (+30 mV),
short while and the membrane potential
so one action potential is not bigger than
becomes more negative, resulting in the
another. Stronger stimuli will initiate multiple
hyperpolarizing overshoot. Then the channel
action potentials more quickly, but the
closes again and the membrane can return to
individual signals are not bigger. Thus, for
the resting potential because of the ongoing
example, you will not feel a greater sensation of
activity of the non-gated channels and the
pain, or have a stronger muscle contraction,
Na+/K+ pump.
because of the size of the action potential
because they are not different sizes.

As we have seen, the depolarization and

repolarization of an action potential are
dependent on two types of channels (the
voltage-gated Na+ channel and the voltage-
gated K+ channel). The voltage-gated
Na+ channel actually has two gates. One is
the activation gate, which opens when the
membrane potential crosses −55 mV. The other
gate is the inactivation gate, which closes after Figure 8. Stages of an Action Potential
a specific period of time—on the order of a
All of this takes place within approximately 2
fraction of a millisecond. When a cell is at rest,
milliseconds (Figure 8). While an action
the activation gate is closed and the inactivation
potential is in progress, another one cannot be
gate is open. However, when the threshold is
initiated. That effect is referred to as
reached, the activation gate opens, allowing
the refractory period. There are two phases of
Na+ to rush into the cell. Timed with the peak of
the refractory period: the absolute refractory
depolarization, the inactivation gate closes.
period and the relative refractory period.
During repolarization, no more sodium can
During the absolute phase, another action
enter the cell. When the membrane potential
potential will not start. This is because of the
passes −55 mV again, the activation gate closes.
inactivation gate of the voltage-gated cell membrane. As the Na+ moves, or flows, a
Na+ channel. Once that channel is back to its short distance along the cell membrane, its
resting conformation (less than −55 mV), a new positive charge depolarizes a little more of the
action potential could be started, but only by a cell membrane. As that depolarization spreads,
stronger stimulus than the one that initiated the new voltage-gated Na+ channels open and more
current action potential. This is because of the ions rush into the cell, spreading the
flow of K+ out of the cell. Because that ion is depolarization a little farther.
rushing out, any Na+ that tries to enter will not
Because voltage-gated Na+ channels are
depolarize the cell, but will only keep the cell
inactivated at the peak of the depolarization,
from hyperpolarizing.
they cannot be opened again for a brief time—
Plotting voltage measured across the cell the absolute refractory period. Because of this,
membrane against time (as shown in Figure 8), depolarization spreading back toward
the events of the action potential can be related previously opened channels has no effect. The
to specific changes in the membrane voltage. action potential must propagate toward the
axon terminals; as a result, the polarity of the
1. At rest, the membrane voltage is
neuron is maintained, as mentioned above.
−70 mV.
Propagation, as described above, applies to
2. The membrane begins to depolarize
unmyelinated axons. When myelination is
when an external stimulus is applied.
present, the action potential propagates
3. The membrane voltage begins a rapid differently. Sodium ions that enter the cell at
rise toward +30 mV. the initial segment start to spread along the
length of the axon segment, but there are no
4. The membrane voltage starts to return voltage-gated Na+ channels until the first node
to a negative value. of Ranvier. Because there is not constant
5. Repolarization continues past the opening of these channels along the axon
resting membrane voltage, resulting in segment, the depolarization spreads at an
hyperpolarization. optimal speed. The distance between nodes is
the optimal distance to keep the membrane still
6. The membrane voltage returns to the depolarized above threshold at the next node.
resting value shortly after As Na+ spreads along the inside of the
hyperpolarization. membrane of the axon segment, the charge
Propagation of the Action Potential starts to dissipate. If the node were any farther
down the axon, that depolarization would have
The action potential is initiated at the beginning fallen off too much for voltage-gated
of the axon, at what is called the initial segment. Na+ channels to be activated at the next node of
There is a high density of voltage-gated Ranvier. If the nodes were any closer together,
Na+ channels so that rapid depolarization can the speed of propagation would be slower.
take place here. Going down the length of the
axon, the action potential is propagated Propagation along an unmyelinated axon is
because more voltage-gated Na+ channels are referred to as continuous conduction; along the
opened as the depolarization spreads. This length of a myelinated axon, it is saltatory
spreading occurs because Na+ enters through conduction. Continuous conduction is slow
the channel and moves along the inside of the because there are always voltage-gated
Na+ channels opening, and more and more
Na+ is rushing into the cell. Saltatory conduction
is faster because the action potential basically
jumps from one node to the next (saltare = “to
leap”), and the new influx of Na+ renews the
depolarized membrane. Along with the
myelination of the axon, the diameter of the
axon can influence the speed of conduction.
Much as water runs faster in a wide river than in
a narrow creek, Na+-based depolarization
spreads faster down a wide axon than down a
narrow one. This concept is known
as resistance and is generally true for electrical
wires or plumbing, just as it is true for axons,
although the specific conditions are different at
the scales of electrons or ions versus water in a
river.