Bioelectricity
Membrane Potentials
• A. The body as a whole is electrically neutral
• B. All of the cells of body have an electrical potential across
their membrane (Voltage difference) known as the
membrane potential
• C. Membrane potentials develop because of differing ion
concentrations between the inside and outside of the cell
Membrane Potentials
Membrane Potentials
• Principals of electricity - Potential difference is determined
by the difference in charge between two points
• 1. Units of electrical potential are in volts (V) or for
biological system millivolts (mV) 1 V = 1000mV
• 2. Voltage is always measured between two points
(Potential difference)
Membrane Potentials
• B. Current - flow of electrical charges from one point to
another
• 1. Like charges repel unlike attract
• 2. Ions tend to move from areas of greater concentration to
areas of least concentration
• 3. Movement of a positive ion from one side of a
membrane to the other implies a negative charge is left
behind
Membrane Potentials
• C. Current Flow
• Ohm’s Law - I = E / R, R = resistance
• I = current flow, E = electrical potential
• 1. Cell - Aqueous solution + good conductor (Ions and water)
• 2. Lipid membrane - A few charged groups can not carry current - high
electrical resistance - good insulator
• 3. ECF and ICF - both have low electrical resistance
Membrane Potentials
• Resting Membrane Potential
•1. By convention - ECF (outside of the cell) is
assigned a voltage of zero
•2. Polarity of the membrane is stated in terms of
the sign of the excess charge inside of the cell
Membrane Ion Channels
• Types of Channels
•1. Leak channels - Open all of the time - slow leak of
ions
•a. Sodium, potassium & chlorine
•b. Membrane 75% more permeable to K+ than Na+
•c. Accounts for 95% of the resting membrane
potential
Membrane Ion Channels
• 2. Na+K+ATPase Pump
• a. Unequal transport of positive ions makes the ICF more negative
than it would be from diffusion alone - 2 K+ inside and 3 Na+ to
outside
• b. Electrogenic pump
• c. Accounts for 5% of resting membrane potential
Membrane Potentials
Ion Gradients
• The ion gradients have two forms.
•1. Chemical Concentration Gradient
•2. Electrical concentration gradient
•(Charge buildup and charge differential)
•Together these form what is known as the
electrochemical gradient
Resting Membrane Potential
• 1. In all cells a potential difference across the membrane exists
• a. Inside is negative (Na+K+ATPase)
• b. Membrane potentials usually within -40 to -90 mv
• 2. A cell with a resting membrane potential is said to be polarized
• 3. Both the inside and the outside of the cell are electrically neutral
Resting Membrane Potential
• B. Factors that determine the resting membrane potential
•Selective permeability of the plasma membrane
•Leak channels
•Na+K+ATPase pump
•Differences in ion concentrations
Membrane Potentials
Resting Membrane Potential
• 2. Many substances are in the cell but the mobile ions Na+, K+, Ca++
and Cl- play the most important roles
• 3. ECF - Cl- helps to balance Na+
• ICF - Proteins (Neg charge) balance K+
Resting Membrane Potential
• 4. Selective membrane permeability
•a. At rest - Slightly permeable to Na+, 75 times
more permeable to K+, and freely permeable to
Cl-
•b. K+ moves down it’s concentration gradient
more easily & faster than Na+
•c. Movement of a K+ out leaves a negative
charge behind
Resting Membrane Potential
• d. Why no equilibrium?
•Na+K+ATPase pump - stabilizes resting membrane
potential by maintaining diffusion gradients for
Na+ and K+
•Concentration gradient – Limit to ability of
Na+K+ATPase pump
• c. Cl- Movement out = movement in - no contribution to
membrane potential
Equilibrium Potential
•Equilibrium potential or electrochemical
potential at which ion movements in both
directions across the membrane are exactly
balanced (net movement = zero)
• 1. Ion flux = 0 implies no net ion movement
• 2. The value of the equilibrium potential (Nernst potential)
for any ion depends on the concentration gradient across
the membrane for that ion
Equilibrium Potential
• 4. The greater the concentration gradient the greater the
equilibrium potential
• 5. The equilibrium potential for one ion can be different in
magnitude and direction from those of other ions
• 6. Given the ion concentration gradient the Nernst
potential for any ion can be calculated. The Nernst
equation is used to determine the electrochemical potential
for any ion across the biological membrane.
Equilibrium Potential
• Nernst Equation
•E(x) = RT/ZF log [x]inside/[x]outside
• R = Gas constant
• T = Temp. degrees Kelvin
• Z = Charge on ion (Valance)
• F = Faraday’s constant
Membrane Potentials
Nernst’s Equation
• A more useful form of the Nernst’s equation is -
•E(x) = -61mV log [X]inside / [X]outside
•or
• = 61 mV log [X]outside / [X]inside
Membrane Potentials
Nernst’s Equation - Examples
• Example 1 - Calculate the electrochemical potential for Na+
• E Na+ = -61mV log [14]/[140]
• log of 0.10 = -1
• then
• E Na+ = 61 mV
Membrane Potentials
Nernst’s Equation - Examples
• Example 2 - Calculate the electrochemical potential for K+
• E K+ = -61mV log [140]/[4]
• log of 35 = 1.5441
• then
• E K+ = - 94 mV
Membrane Potentials
Nernst Equation - Examples
Membrane Potentials
Resting Membrane Potential
• In reality a living cell contains a great number of ionic species. Most
of these can and do move in and out of the cell with the help of
proteins. The net movement of all ionic currents across the
membrane determines the resting membrane potential.
Membrane Potentials
Resting Membrane Potential
• The net current flow ( I ) across the membrane is given by;
• I(x) = g(x) {Em - E(x)}
• Where - g(x) is ion conductance
•Em is resting membrane Potential
•E(x) is the Nernst’s Potential
Membrane Potentials
Resting Membrane Potential
• At rest the membrane potential is not changing, then the sum of all
currents must equal zero.
• Thus
•I Na+ + I K+ + I Cl- + … = 0
Membrane Potentials
Resting Membrane Potential
• Therefore
•g Na+[Em -ENa+] + g K+[Em - EK+] + g Cl-[Em - ECl-] + … = 0
Membrane Potentials
Resting Membrane Potential
• Solving for Em yields the Goldman equation which gives the resting
membrane potential
Membrane Potentials
Resting Membrane Potential
• Goldman Equation
• Em = [gNa+/(gNa+ + gK+ + gCl- )] E Na+
• + [gK+/(gNa+ + gK+ + gCl- )] E K+
• + [gCl-/(gNa+ + gK+ + gCl- )] E Cl-
• +…
• Thus the resting membrane potential is a summation of all of the ion
potentials times their percentage of the total ion conductance
Membrane Potentials
Resting Membrane Potential
• Since K+ conductance is almost 75 times that of Na+. The
resting membrane potential is much closer to the Nernst’s
potential for K+ than it is to the Nernst’s potential for Na+.
• Why would K+ conductance predominate?
Excitable Cells
• A. Nerve and muscle cells are excitable (Em < -40 mV)
•1. Electrochemical impulses are transient and
rapid changes in Em
•2. Two forms of electrochemical impulses
• B. Electrochemical signals
•1. Graded potentials - short distance
•2. Action potentials - long distance
A typical neuron
(Note – the term ‘nerve’ can refer to collections of
neurons)
The giant axon of squid
• Axons up to 1mm in diameter – 1000 times that of mammalian
nerves
• Hodgkin and Huxley (1939) measured resting potential
• Hodgkin and Katz (1949) measured change in potential
resulting from manipulating K+ concentration
• Permeability to potassium is the primary source of the resting
membrane potential (NB permeability due to different process from
gates)
Ionic gradients maintain electrical potentials
• Electrical potentials across cell membranes are generated by
differences in concentration of specific ions (K+, Na+, Cl-) which are
maintained by ion transporters (use energy for energetically
unfavourable reaction)
Absolute temp Permeability of membrane to ion
Gas constant
Concentration of ion
Voltage
Faraday constant
Ratio of outside to inside
Goldman equation (from Nernst equation)
Ion Intracellular Extracellular
Potassium 400 20
Concentrations in a squid giant axon – Sodium 50 440
the resting potential is -65mV Chloride 4-150 560
Calcium 0.0001 10
Electrical signals are generated by ionic
movement
• The resting potential is maintained by active transport of ions (e.g. the Na/K pump – 2 K+
pumped in and 3 Na+ out for one ATP).
• Electrical signals occur when selective ion channels open to allow specific ions to move down
gradient
• Depolarisation largely caused by change in permeability to Na + ions
Action potentials in the squid giant axon
Electrical signals are propagated by voltage-dependent channels
• A threshold depolarisation causes adjacent sodium channels to open
• Signals move along axons
The properties of single ion channels can be observed and manipulated using the patch-clamp
method
Myelinated nerve cells have much faster rates of transmission
Passive diffusion of Na+ ions triggers voltage-dependent gates at the next node of Ranvier
Increases speed of action potential from 1m/s to about 18 m/s in mammalian nerves
Nerve cells communicate via synapses
• Electrical synapses via gap junctions between cells allow direct passage of
electrical signal
• Chemical synapses enable communication by the release of
neurotransmitters
• Neurotransmitters in pre-synaptic vesicles
• Release triggered by Ca2+ influx through voltage-gated channels
• Chemical diffuse across synapse and recognised by receptors
• Threshold response in post-synaptic nerve
• Computation through pre- and post-synaptic modification
• A similar process allows communication between nerves and effectors
• e.g. acetylcholine released at nerve-muscle end plates
The diversity of neurotransmitters
• Over 100 neurotransmitters
• Two classes of neurotransmitter
• Neuropeptides: 3-36 amino acid peptides such as α- and β-endorphins
• Small-molecule neurotransmitters including amino acids (glutamate, aspartate), purines (ATP) and
biogenic amines such as serotonin, dopamine and histamine
• Examples
• Acetylcholine at neuromuscular junctions
• Glutamate is the most important transmitter for normal brain function
• Drugs and disease
• Most psychotrophic drugs alter steps in the generation and release of neurotransmitters (e.g.
fluoxetine – Prozac – blocks reuptake of serotonin)
Nerve cells are stimulated by diverse receptor mechanisms
• Somatic sensory receptors
• E.g. Muscle spindles, Merkel’s discs, Meissner’s corpuscles
• Pain receptors
• Visual/photoperiod receptors
• Retina, pineal gland
• Auditory receptors
• Cochlea
• The vestibular system
• Otolith organs (utricle and sacculus) and semicircular canals of the inner ear
• Chemical receptors
• Olfaction, taste, trigeminal chemsonsory system
• The conversion of signal to nervous response is called signal transduction
Hodgkin-Huxley Model
and
FitzHugh-Nagumo Model
Nervous System
• Signals are propagated from nerve cell to nerve cell
(neuron) via electro-chemical mechanisms
• ~100 billion neurons in a person
• Hodgkin and Huxley experimented on squids and
discovered how the signal is produced within the
neuron
• H.-H. model was published in Jour. of Physiology
(1952)
• H.-H. were awarded 1963 Nobel Prize
• FitzHugh-Nagumo model is a simplification
Neuron
C. George Boeree: [Link]/~cgboeree/
Action Potential
mV
Axon membrane
_ 30 potential difference
V = V i – Ve
When the axon is
_0
excited, V spikes
V because sodium
Na+ and potassium
K+ ions flow
through the
membrane.
10 msec
-70
Nernst Potential
VNa , VK and Vr
Ion flow due to
electrical signal
Traveling wave
C. George Boeree: [Link]/~cgboeree/
Circuit Model for Axon Membrane
Since the membrane separates charge, it is modeled as a
capacitor with capacitance C. Ion channels are resistors.
1/R = g = conductance
iC = C dV/dt
iNa = gNa (V – VNa)
iK= gK (V – VK)
ir = gr (V – Vr)
Circuit Equations
Since the sum of the currents is 0, it follows that
where Iap is applied current. If ion conductances are constants
then group constants to obtain 1st order, linear eq
Solving gives
Variable Conductance
g
Experiments showed that gNa and gK varied with time and V. After
stimulus, Na responds much more rapidly than K .
Hodgkin-Huxley System
Four state variables are used:
v(t)=V(t)-Veq is membrane potential,
m(t) is Na activation,
n(t) is K activation and
h(t) is Na inactivation.
In terms of these variables gK=gKn4 and gNa=gNam3h.
The resting potential Veq≈-70mV. Voltage clamp experiments
determined gK and n as functions of t and hence the parameter
dependences on v in the differential eq. for n(t). Likewise for m(t)
and h(t).
Hodgkin-Huxley System
110 mV
Iap =8, v(t)
1.2
m(t)
n(t)
40msec
h(t)
10msec
Iap=7, v(t)
Fast-Slow Dynamics
m(t)
ρm(v) dm/dt = m∞(v) – m.
ρm(v) is much smaller than
n(t) ρn(v) and ρh(v). An increase in
v results in an increase in m∞
(v) and a large dm/dt. Hence
Na activates more rapidly
h(t) than K in response to a
change in v.
10msec
v, m are on a fast time scale and n, h are slow.
FitzHugh-Nagumo System
and
I represents applied current, ε is small and f(v) is a cubic nonlinearity. Observe that in the (v,w)
phase plane
which is small unless the solution is near f(v)-w+I=0. Thus the slow manifold is the cubic
w=f(v)+I which is the nullcline of the fast variable v. And w is the slow variable with nullcline w=2v.
Take f(v)=v(1-v)(v-a) .
Stable rest state I=0 Stable oscillation I=0.2
w w
v v
Web resources
• [Link]