Module 4: BioElectrical Properties

Topic 1: Conduction of Electrical Activity, Spread of Electrical Signals

1. Introduction
 Neurons and excitable cells (e.g., muscle) use electrical activity to transmit information.
 This depends on:
o Ion gradients (Na⁺, K⁺, Cl⁻, Ca²⁺) set by pumps and channels.
o Resting membrane potential (RMP).
o Action potentials (APs) and their propagation along membranes.
 Signal conduction allows rapid communication over long distances.

2. Electrical Properties of the Membrane

 Membrane acts like an electrical circuit:
o Capacitance (Cm): Lipid bilayer stores charge.
o Resistance (Rm): Ion channels determine conductance.
o Axial resistance (Ra): Cytoplasmic resistance to current flow.
 The interaction of these parameters governs how far and how fast signals spread.

3. Passive Spread of Electrical Signals

 Sub-threshold stimuli (below AP threshold) cause electrotonic (graded) potentials.
 Features:
o Spread is local and decays with distance.
o Described by cable theory.

 Length constant (λ): λ=

√ Rm
Ra

o Determines how far a signal can travel before decaying significantly.

o Larger λ → longer-distance passive spread.
Example: Dendrites rely on passive spread of postsynaptic potentials to reach axon hillock.

4. Active Conduction: The Action Potential

 Passive spread alone is insufficient for long-distance signaling.
 Action potentials are regenerative, self-propagating waves of depolarization.
 Mechanism:
1. Stimulus depolarizes membrane beyond threshold.
2. Voltage-gated Na⁺ channels open → Na⁺ influx → depolarization.
 3. Na⁺ channels inactivate; K⁺ channels open → K⁺ efflux → repolarization.
4. Refractory period ensures unidirectional propagation.

5. Conduction of Action Potentials

5.1 Continuous Conduction (Unmyelinated fibers)
 Every adjacent region of membrane depolarizes sequentially.
 Slower, energy-demanding (more Na⁺/K⁺ pumping needed).
5.2 Saltatory Conduction (Myelinated fibers)
 In myelinated axons (vertebrates):
o Myelin (Schwann cells, oligodendrocytes) insulates axon → reduces leakage (↑Rm).
o Action potentials regenerate only at nodes of Ranvier (gaps in myelin).
o Electrical signal “jumps” node-to-node → very rapid conduction.
 Conduction velocity can exceed 100 m/s.

6. Factors Affecting Conduction Velocity

 Axon diameter: Larger diameter → lower axial resistance → faster conduction (seen in squid giant
axon).
 Myelination: Increases speed (saltatory conduction).
 Temperature: Higher temp → faster kinetics of channels (within physiological range).
 Channel density: High density of Na⁺ channels at nodes ensures rapid depolarization.

7. Spread of Electrical Signals in Neurons

 Dendrites: Receive synaptic input → passive spread (EPSPs, IPSPs).
 Axon hillock: Integrates inputs → if threshold reached → action potential triggered.
 Axon: AP propagates actively along axon → signal transmitted to terminals.
 Synaptic terminals: Depolarization opens Ca²⁺ channels → neurotransmitter release.

8. Physiological & Clinical Relevance

 Myelination disorders:
o Multiple sclerosis (MS) → demyelination → slowed conduction.
o Guillain–Barré syndrome → peripheral nerve demyelination.
 Anesthetics (lidocaine, tetrodotoxin): Block voltage-gated Na⁺ channels → prevent conduction.
 Hyperkalemia / hypokalemia: Alter excitability by shifting RMP closer to or farther from
threshold.
9. Summary Table

Property Passive Spread Action Potential Conduction

Mechanism Local ion current Regenerative Na⁺/K⁺ currents

Distance Short (decays with λ) Long (non-decremental)

Speed Fast local spread, but limited Slower (unmyelinated) / very fast (myelinated)

Role Dendrites, synaptic potentials Axons, signal transmission

Key Concept:
 Passive spread = fast but limited in distance (graded potentials).
 Active conduction (APs) = slower to start but self-sustaining, long-distance, non-decremental.
 Myelination + large axon diameter → increase conduction velocity dramatically.
Topic 2: Donnan Equilibrium

1. What is Donnan Equilibrium?

 Also called the Gibbs–Donnan effect.
 Describes the distribution of permeant ions across a semipermeable membrane when
impermeant charged molecules are present on one side.
 Typical example:
o Inside of cells: large negatively charged macromolecules (proteins, nucleic acids) that cannot
cross the membrane.
o These influence the equilibrium distribution of diffusible ions (Na⁺, K⁺, Cl⁻).
Key Idea: Impermeant ions “trap” permeant ions in such a way that electrochemical equilibrium is
reached but electroneutrality is maintained.

2. Experimental Setup
Imagine a membrane separating two compartments:
 Compartment A (inside cell): Contains impermeant negatively charged proteins (Pr⁻).
 Compartment B (outside): No impermeant proteins.
 Both compartments contain permeant ions (Na⁺, Cl⁻).
 Membrane is permeable to Na⁺ and Cl⁻, but impermeable to Pr⁻.

3. Ionic Distribution at Equilibrium

At Donnan equilibrium:
 [Cl⁻] is lower inside than outside (repelled by intracellular proteins).
 [Na⁺] is higher inside than outside (balances negative charges).
 This leads to a potential difference across the membrane — the Donnan potential.
General condition (equilibrium law):
¿¿
i.e., the product of diffusible cation and anion concentrations is equal on both sides.

4. Properties of Donnan Equilibrium

1. Electroneutrality:
o Each compartment remains electrically neutral (total + charges = total – charges).
2. Unequal ion distribution:
o Concentrations of permeant ions differ across membrane.
3. Osmotic imbalance:
 o More total solute particles inside → drives water influx → tendency for cell swelling.
4. Resting potential contribution:
o Donnan effect contributes to negative resting potential of cells.

5. Biological Implications
 Cells:
o Intracellular proteins (impermeant anions) create Donnan forces.
o Na⁺/K⁺ ATPase pump counteracts osmotic swelling predicted by Donnan equilibrium.
 Red Blood Cells:
o Without active ion pumping, RBCs would swell and lyse due to Donnan-driven osmotic
imbalance.
 Cartilage & Connective Tissue:
o Proteoglycans carry negative charges → attract Na⁺ → draw in water → maintain tissue
hydration.
 Plant Cells:
o Donnan equilibrium contributes to turgor pressure.

6. Clinical Relevance
 Edema: Accumulation of negatively charged plasma proteins in interstitial spaces → draws water →
swelling.
 Kidney disease / liver disease: Altered protein balance in plasma disturbs Donnan forces → fluid
imbalance.
 Dialysis: Based on principles of diffusion and Donnan equilibrium (impermeant plasma proteins
influence solute shifts).

7. Comparison to Nernst Potential

 Nernst Equation: Describes equilibrium potential for a single permeant ion.
 Donnan Equilibrium: Describes equilibrium distribution of multiple permeant ions in presence of
impermeant ions.

8. Quick Recap Table

Feature Donnan Equilibrium

Impermeant ions Required (e.g., proteins)

Permeant ions Redistribute unequally

Electroneutrality Maintained in each compartment

Feature Donnan Equilibrium

Osmotic effect Water influx → swelling risk

Biological importance Resting potential, turgor, tissue hydration

Key Concept:
Donnan equilibrium arises because impermeant ions trap diffusible ions, leading to unequal ion distribution
and an osmotic pressure gradient. Cells must use ion pumps (Na⁺/K⁺ ATPase) to counterbalance this effect
and maintain stable volume.
Topic 3: The Resting Membrane Potential

1. Definition
 The resting membrane potential (RMP) is the steady voltage difference across the plasma
membrane of a cell at rest (not firing an action potential).
 Typical values:
o Neurons: −60 to −70 mV
o Skeletal muscle: −90 mV
o Plants/fungi: around −120 mV
RMP is always negative inside relative to outside.

2. Origin of Resting Membrane Potential

RMP arises from three main factors:
2.1 Ion Concentration Gradients
 Maintained by active transport (mainly Na⁺/K⁺ ATPase).
 Typical mammalian neuron:
o High K⁺ inside (~140 mM), low outside (~5 mM).
o High Na⁺ outside (~145 mM), low inside (~15 mM).
o High Cl⁻ outside (~110 mM), low inside (~10 mM).
2.2 Selective Membrane Permeability
 At rest, the membrane is much more permeable to K⁺ (due to K⁺ leak channels) than to Na⁺ or
Cl⁻.
 Therefore, RMP is closer to E_K (equilibrium potential for K⁺) than to E_Na.
2.3 Electrogenic Pumps
 Na⁺/K⁺ ATPase: moves 3 Na⁺ out, 2 K⁺ in → creates net loss of + charge inside → contributes to
negative RMP.
 In plants/fungi: H⁺ ATPase pumps protons out → generates negative inside potential.

3. Electrochemical Driving Forces

 Each ion’s movement depends on:
o Chemical gradient (concentration difference).
o Electrical gradient (voltage across membrane).
 Together = Electrochemical gradient.
 At equilibrium, electrical and chemical forces are balanced:
 RT [ion]outside
Eion = ln ( )
zF [ion ]inside

→ Nernst Equation.

4. Quantitative Description
4.1 Nernst Potential
 Describes equilibrium potential for a single ion.
 Example (37°C, K⁺):
E K =61mV ⋅log ¿ ¿

4.2 Goldman-Hodgkin-Katz (GHK) Equation

 For multiple ions: V m =61mV ⋅log ¿ ¿
 Incorporates relative permeabilities (P) for K⁺, Na⁺, Cl⁻.
 Explains why RMP is closer to E_K but slightly depolarized due to Na⁺ and Cl⁻.

5. Physiological Significance of RMP

 Electrical excitability: Basis for action potentials in neurons, muscle, cardiac cells.
 Signal integration: Determines responsiveness to synaptic inputs.
 Transport processes: Drives secondary active transport (e.g., Na⁺/glucose symporter).
 Cell survival: Maintains osmotic balance (counteracts Donnan forces).

6. Clinical Relevance
 Hyperkalemia (↑[K⁺]out):
o Reduces K⁺ efflux, depolarizes RMP → increases excitability → arrhythmias.
 Hypokalemia (↓[K⁺]out):
o Hyperpolarizes RMP → decreases excitability → muscle weakness.
 Cardiac glycosides (e.g., digoxin):
o Inhibit Na⁺/K⁺ ATPase → alter RMP → affect heart contractility.
 Demyelinating diseases (MS, GBS):
o Impaired conduction due to altered RMP stability.

7. Summary Table
Factor Role in RMP

Creates gradients, electrogenic (3 Na⁺ out, 2 K⁺

Na⁺/K⁺ ATPase
in)

K⁺ Leak Channels Main contributor to negative RMP

Cl⁻ Permeability Helps fine-tune RMP

Impermeant anions (Pr⁻) Contribute to Donnan effect

Goldman Equation Describes RMP considering multiple ions

Key Concept:
The resting membrane potential is mainly set by K⁺ diffusion potential, slightly modified by Na⁺/Cl⁻ leak
and electrogenic pumps. It provides the electrical baseline for excitability and signal transmission.
Topic 4: Nernst & Goldman Equations

1. Nernst Equation
1.1 Purpose
 Predicts the equilibrium potential (Eion) for a single ion.
 The potential at which there is no net movement of that ion across the membrane because chemical
and electrical driving forces are balanced.

1.2 Formula
RT
Eion = ln ¿
zF
At 37°C (310 K), this simplifies to:

1 [ion ]outside
Eion =61 mV ⋅ log (¿ )¿
z [ion] inside

where:
 Eion = equilibrium potential for ion (mV)

 R = gas constant (8.314 J·mol⁻¹·K⁻¹)

 T = absolute temperature (K)
 F = Faraday constant (96,485 C/mol)
 z = valence (charge) of the ion
 [[ion] outside, [ion]inside = extracellular & intracellular concentrations
1.3 Interpretation
 If V m =Eion , no net flux of that ion.

 If V m ≠ Eion , ion moves to drive V m toward Eion .

Example (K⁺ in neurons):
 ¿¿
 E K ≈−90 mV

 Since resting potential (≈ -70 mV) is more positive than E K , K⁺ efflux occurs.

2. Goldman-Hodgkin-Katz (GHK) Equation

2.1 Purpose
 Extends Nernst equation to account for multiple ions and their relative permeabilities.
 Describes the resting membrane potential (V m).
2.2 Formula
V m =61mV ⋅log ¿ ¿

where:
 Pion = membrane permeability for that ion

 [ion]¿ ,[ion ]out = intracellular & extracellular concentrations

Note: For anions (Cl⁻), inside/outside terms are flipped because of negative charge.

2.3 Interpretation
 If P K ≫ P Na , PCl, then V m ≈ E K .
 In reality:
o P K dominates (many leak channels).

o Small but significant contributions from Na⁺ and Cl⁻ shift V m slightly positive (from -90 mV
toward -70 mV).

3. Key Differences Between Nernst & Goldman

Feature Nernst Equation Goldman Equation

Ions considered Single ion Multiple ions simultaneously

Condition Equilibrium (no net ion flux) Steady-state (net current = 0, ions still moving)

Use Equilibrium potential (Eion) Resting membrane potential (Vm)

4. Physiological Significance
 Nernst equation:
o Predicts reversal potential of ion channels.
o Explains direction of ionic currents during action potential.
 GHK equation:
o Explains why RMP ≈ -70 mV, not equal to E K (-90 mV).
o Used to calculate steady-state voltage from real ionic gradients.

5. Clinical Relevance
 Hyperkalemia (↑[K⁺]out):
o Makes E K less negative → depolarizes cells → hyperexcitability → arrhythmias.
 Hypokalemia (↓[K⁺]out):
o Makes E K more negative → hyperpolarizes cells → muscle weakness.
  Anesthetics & channel blockers:
o Shift permeabilities ( P Na , P K ), altering Vm and excitability.

Key Concept:
 Nernst: equilibrium potential of one ion.
 Goldman: resting potential considering all ions + permeabilities.
Topic 5: Hodgkin–Katz Experiment

1. Historical Context
 Early 20th century: It was known that neurons had a negative resting potential, but the exact ionic
basis was unclear.
 In the 1930s–40s, Alan Hodgkin (UK physiologist) studied giant axons of squid (large enough for
electrodes).
 Bernard Katz (German-British physiologist) collaborated with Hodgkin to measure ion fluxes.
 They developed a quantitative description of the resting membrane potential (V m) using ion
gradients and permeabilities → now called the Goldman–Hodgkin–Katz (GHK) equation.

2. Experimental Setup
 Used squid giant axon (~1 mm diameter → easy to insert electrodes).
 Measured intracellular and extracellular ionic concentrations (Na⁺, K⁺, Cl⁻).
 Used voltage electrode techniques to record membrane potentials.
 Manipulated external [K⁺], [Na⁺], [Cl⁻] to test the effect on Vm.

3. Key Findings
1. Resting Membrane Potential is Mostly K⁺-Dependent
o Changing [K⁺]outside caused predictable shifts in V m.

o V m moved toward the Nernst potential for K⁺ ( E K ).

o Concluded: At rest, membrane is much more permeable to K⁺ than to Na⁺.

2. Na⁺ and Cl⁻ Also Contribute
o Small but significant depolarization shifts showed that Na⁺ permeability is nonzero at rest.
o Cl⁻ distribution is also important in fine-tuning V m.
3. Electrogenic Pump Contribution
o Evidence for the Na⁺/K⁺ ATPase contributing to resting potential (3 Na⁺ out, 2 K⁺ in).
4. Development of the Hodgkin–Katz Equation
o Derived from Goldman’s constant-field equation, incorporating permeabilities (P) of K⁺,
Na⁺, Cl⁻.
V m =61mV ⋅log ¿ ¿

 This explained why V m ≈ −70 mV instead of exactly equal to E K (−90 mV).

4. Significance of the Hodgkin–Katz Work

  Provided the first quantitative model linking ion concentrations, membrane permeability, and
membrane potential.
 Showed that resting potential is not equilibrium, but a steady-state:
o Ions still move (Na⁺ leaks in, K⁺ leaks out).
o Steady-state maintained by Na⁺/K⁺ ATPase.
 Laid foundation for Hodgkin–Huxley model (1952): Described dynamic ionic currents underlying
the action potential.

5. Nobel Prize
 Hodgkin & Huxley shared the 1963 Nobel Prize in Physiology/Medicine with John Eccles for
discoveries on ionic mechanisms of excitation and inhibition.
 Katz also received a Nobel Prize (separately, for synaptic transmission).

6. Clinical & Physiological Importance

 Understanding of:
o Resting potential in neurons, muscle, and heart.
o Abnormal excitability in hyperkalemia, hypokalemia.
o Basis for drug action (e.g., anesthetics blocking Na⁺ channels).

7. Quick Recap Table

Concept Hodgkin–Katz Finding

RMP origin Mainly K⁺ diffusion

Role of Na⁺ Small inward leak → V m depolarized from EK

Role of Cl⁻ Helps stabilize V m

Na⁺/K⁺ ATPase Maintains gradients, contributes to negativity

Equation outcome GHK equation predicts V m ~ −70 mV

Key Concept:
The Hodgkin–Katz experiments demonstrated that the resting membrane potential results from selective
permeability to K⁺, small contributions from Na⁺ & Cl⁻, and active ion pumping. This was the
experimental proof behind the Goldman equation.
Topic 6: Voltage Clamp, Membrane Impedance, Capacitance

1. Voltage Clamp Technique

1.1 Purpose
 Developed by Kenneth Cole (1949), later perfected by Hodgkin & Huxley.
 Allows scientists to “clamp” the membrane potential at a chosen value and measure ionic currents.
 Essential for discovering the ionic basis of the action potential.

1.2 Principle
 In a normal cell, membrane potential (V m) changes when ionic currents flow.
 In voltage clamp:
1. Command voltage (V c ) is set by experimenter.

2. V m is continuously compared to V c .

3. A feedback amplifier injects current to keep V m = V c .

4. The injected current is equal and opposite to the ionic current across the membrane → can be
measured directly.

1.3 Discoveries
 Using voltage clamp in squid axon:
o Depolarization → inward Na⁺ current (fast, transient).
o Followed by outward K⁺ current (delayed, sustained).
 Led to Hodgkin–Huxley model of voltage-gated channels.

2. Membrane Impedance
2.1 Definition
 Impedance (Z): The overall resistance of the membrane to alternating current (AC), including both
resistive (ion channels) and capacitive (lipid bilayer) properties.
 Analogous to electrical circuits:
o Resistors (R): Ion channels (conductance pathways).
o Capacitors (C): Lipid bilayer (charge storage).
2.2 Properties
 Membrane impedance varies with frequency:
o At low frequency → capacitance dominates (slow charge/discharge).
o At high frequency → resistance dominates (channels conduct).
  Studied using electrical impedance spectroscopy.
2.3 Biological Significance
 Impedance affects signal propagation in dendrites and axons.
 Low impedance → fast signal spread.
 High impedance → electrical isolation, compartmentalization of signals.

3. Membrane Capacitance
3.1 Definition
 The ability of the cell membrane to store electrical charge.
 Lipid bilayer acts as a thin capacitor:
o Insulating layer (lipids) separates two conductive fluids (ICF, ECF).
3.2 Equation
εA
C m=
d
where:
 C m = membrane capacitance (farads, typically ~1 µF/cm²)

 ε = dielectric constant of lipid (~2–3)

 A = membrane area
 d = membrane thickness (~5 nm)
3.3 Functional Roles
 Charge storage: Small ions accumulate on each side of bilayer.
 Time constant (τ):
τ =Rm ⋅C m

o Determines how fast a membrane can depolarize or repolarize.

o Large τ → slower response, more integration.
 Spatial summation: Capacitance influences how graded potentials combine in dendrites.

4. Physiological & Experimental Relevance

 Voltage clamp: Revealed distinct Na⁺ and K⁺ currents underlying action potentials.
 Impedance: Helps predict signal decay along dendrites (cable theory).
 Capacitance: Determines how much current is needed to change Vm (e.g., larger cells need more
charge).
 Pathology: Demyelination (e.g., multiple sclerosis) increases capacitance and slows conduction.
5. Quick Recap Table

Concept Definition Importance

Voltage clamp FixV m, measure ionic currents Basis of HH model

Opposition to AC (resistance +
Membrane impedance Signal spread, dendritic processing
capacitance)

Membrane Charge storage ability of bilayer (~1 Time constant, excitability, conduction
capacitance µF/cm²) speed

Key Concept:
 Voltage clamp → experimental tool to dissect ionic currents.
 Impedance → how the membrane resists/filters signals.
 Capacitance → charge storage, determines timing of potential changes.
Topic 7: Transmembrane & Electrochemical Potential

1. Transmembrane Potential
1.1 Definition
 The voltage difference across a cell membrane, usually expressed as:
V m =V ¿−V out

 For most cells, inside is negative relative to outside (neurons ≈ −60 to −70 mV).

1.2 Basis of Transmembrane Potential

1. Ion concentration gradients
o Maintained by active pumps (e.g., Na⁺/K⁺ ATPase).
o K⁺ high inside, Na⁺ and Cl⁻ high outside.
2. Selective membrane permeability
o Leak channels (esp. K⁺) dominate → V m closer to E K .
3. Electrogenic pumps
o Na⁺/K⁺ pump moves 3 Na⁺ out, 2 K⁺ in → contributes to negativity.
- Transmembrane potential = resting potential in steady state.

2. Electrochemical Potential
2.1 Definition
 The free energy change driving ion movement across the membrane.
 Combines:
o Chemical potential (concentration gradient).
o Electrical potential (voltage gradient).

2.2 Formula
0
μi=μ i + RT ln ⁡[C i]+ zi FΨ

where:
 μi = electrochemical potential of ion iii  [Ci ] = ion concentration

 0
μi = standard potential  z i = valence (charge)

 R = gas constant (8.314 J·mol⁻¹·K⁻¹)  F = Faraday constant (96,485 C/mol)

 T = absolute temperature (K)  Ψ = membrane potential

Key: Electrochemical potential determines whether ion flow is passive (downhill) or requires energy
(uphill).

3. Nernst Potential (Equilibrium Potential)

 At equilibrium, electrochemical potential difference for an ion = 0.
 Leads to Nernst equation:
RT
Eion = ln ¿
zF
 Predicts the voltage at which there is no net flux of that ion.

4. Relationship Between Vm and Electrochemical Potential

 If Vm=Eion → no net ion movement.
 If Vm>Eion → direction of movement depends on charge and gradients:
o For cations: move inward if Vm < Eion, outward if Vm > Eion.
o For anions: opposite logic applies.
Example (neuron):
 Vm ≈ −70 mV
 E_K ≈ −90 mV → K⁺ tends to leave (driving force outward).
 E_Na ≈ +60 mV → Na⁺ tends to enter (driving force inward).
 Net effect = steady state with Na⁺ influx, K⁺ efflux, stabilized by Na⁺/K⁺ ATPase.

5. Physiological Importance
 Signal transmission:
o Action potentials depend on electrochemical gradients of Na⁺ and K⁺.
 Synaptic transmission:
o Ca²⁺ influx (electrochemical gradient) triggers neurotransmitter release.
 Transport processes:
o Electrochemical Na⁺ gradient drives secondary active transport (e.g., Na⁺/glucose
symporter).
 Cell survival:
o Electrochemical balance prevents swelling/shrinkage (counteracts Donnan effect).

6. Clinical Relevance
 Hyperkalemia: Raises extracellular K⁺ → depolarizes Vm (closer to 0) → risk of arrhythmia.
 Hypokalemia: Lowers extracellular K⁺ → hyperpolarizes Vm → muscle weakness.
  Channelopathies: Mutations altering ion conductance disturb electrochemical driving forces
(epilepsy, long QT syndrome).
 Cardiac drugs (digoxin): Inhibit Na⁺/K⁺ ATPase → alters electrochemical gradients → increases
contractility.

7. Quick Recap Table

Concept Definition Equation

Transmembrane
Voltage difference across cell membrane (Vm) V m =V ¿−V out
Potential

Electrochemical Free energy for ion movement (chemical +

μ = μ⁰ + RT ln[C] + zFΨ
Potential electrical)

Nernst Potential Vm at which no net ion flux occurs Eion =(RT / zF)ln([out ]/[¿])

Key Concept:
 Transmembrane potential = actual voltage across membrane.
 Electrochemical potential = driving force for ion movement.
 Balance of both defines resting potential, excitability, and transport processes.
Topic 8: Chemical Synapse & Post-Synaptic Potential

1. Introduction
 Synapse: Specialized junction for communication between neurons or between a neuron and an
effector (e.g., muscle, gland).
 Two types:
o Electrical synapse: Direct ion flow via gap junctions (fast, bidirectional).
o Chemical synapse: Neurotransmitter-mediated (slower, unidirectional, modifiable).
 Here we focus on chemical synapses → predominant in vertebrate nervous system.

2. Structure of a Chemical Synapse

1. Presynaptic terminal (axon bouton)
o Contains synaptic vesicles filled with neurotransmitter.
o Dense active zones with voltage-gated Ca²⁺ channels.
2. Synaptic cleft (~20–40 nm gap)
o Extracellular space where neurotransmitter diffuses.
3. Postsynaptic membrane
o Contains ligand-gated ion channels (ionotropic receptors) or G-protein coupled receptors
(metabotropic).
o Specialized region = postsynaptic density (PSD).

3. Events at the Chemical Synapse

1. Action potential arrives at presynaptic terminal.
2. Depolarization opens voltage-gated Ca²⁺ channels → Ca²⁺ influx.
3. Ca²⁺ triggers vesicle fusion with membrane via SNARE proteins.
4. Neurotransmitter release (exocytosis) into synaptic cleft.
5. Neurotransmitter binds postsynaptic receptors → opens channels.
6. Ionic currents flow → postsynaptic potentials (EPSPs or IPSPs).
7. Termination mechanisms:
o Enzymatic breakdown (e.g., ACh by acetylcholinesterase).
o Reuptake into presynaptic terminal (e.g., dopamine, serotonin).
o Diffusion away.
4. Post-Synaptic Potentials (PSPs)
4.1 Excitatory Postsynaptic Potential (EPSP)
 Caused by opening of cation channels (Na⁺, sometimes Ca²⁺).
 Results in depolarization of postsynaptic membrane.
 Moves Vm closer to threshold for action potential.
 Example: Glutamate (AMPA/NMDA receptors), Acetylcholine (nicotinic receptors).
4.2 Inhibitory Postsynaptic Potential (IPSP)
 Caused by opening of anion (Cl⁻) channels or K⁺ channels.
 Results in hyperpolarization (more negative Vm) or shunting inhibition.
 Moves Vm farther from threshold.
 Example: GABA (GABA_A receptors), Glycine receptors.

5. Integration of PSPs
 A single PSP is usually small (0.2–2 mV), not enough to trigger an AP.
 Neurons integrate multiple PSPs at axon hillock:
1. Spatial summation → multiple synapses active simultaneously.
2. Temporal summation → rapid succession of PSPs at same synapse.
3. EPSPs + IPSPs dynamically balance to determine whether threshold is reached.

6. Synaptic Plasticity
 Synapses are not fixed → can strengthen or weaken with activity.
 Short-term changes: Facilitation, depression, potentiation (ms–min).
 Long-term changes: Long-Term Potentiation (LTP) and Long-Term Depression (LTD).
 Basis for learning and memory (especially in hippocampus).

7. Clinical & Pharmacological Relevance

 Neurotoxins: o Benzodiazepines (enhance
GABA_A receptor IPSPs).
o Botulinum toxin (blocks ACh
release). o NMDA receptor antagonists
(ketamine, anesthetics).
o Tetanus toxin (blocks inhibitory
neurotransmitter release).  Diseases:
 Drugs: o Myasthenia gravis (autoantibodies
to ACh receptors).
o SSRIs (block serotonin reuptake).
o Epilepsy (excess excitation,
reduced inhibition).
8. Quick Recap Table

Feature EPSP IPSP

Main ions Na⁺ (± Ca²⁺) influx Cl⁻ influx, K⁺ efflux

Effect on Vm Depolarization Hyperpolarization/shunting

NT examples Glutamate, ACh (nicotinic) GABA, Glycine

Functional role Increases excitability Decreases excitability

Key Concept:
 Chemical synapses transform electrical signals into chemical ones, then back into electrical
responses.
 PSPs (EPSPs, IPSPs) are graded potentials that integrate to determine neuronal output (AP or no
AP).
Topic 9: Properties of Action Potential

1. Definition
 An action potential (AP) is a rapid, transient, regenerative electrical signal that propagates along
excitable membranes (neurons, muscle, cardiac cells).
 Function: enables long-distance, non-decremental communication.

2. Phases of Action Potential

1. Resting state
o Vm ≈ −70 mV (neurons).
o High K⁺ permeability via leak channels.
2. Depolarization (rising phase)
o Stimulus reaches threshold (~ −55 mV).
o Voltage-gated Na⁺ channels open → rapid Na⁺ influx.
o Vm approaches E_Na (+60 mV).
3. Overshoot
o Vm becomes positive (inside > outside).
o Peak typically +30 to +40 mV.
4. Repolarization (falling phase)
o Na⁺ channels inactivate.
o Voltage-gated K⁺ channels open → K⁺ efflux.
o Vm returns toward E_K (−90 mV).
5. Afterhyperpolarization (undershoot)
o Vm goes slightly below resting (closer to E_K).
o Due to prolonged K⁺ conductance.
6. Restoration
o K⁺ channels close, Vm stabilizes at RMP.
o Na⁺/K⁺ ATPase restores ion gradients.

3. Key Properties
3.1 All-or-None Principle
 AP is triggered only if threshold is reached.
 Subthreshold stimuli → no AP.
 Suprathreshold → AP of same amplitude.
3.2 Threshold
 Minimum depolarization needed to open sufficient Na⁺ channels for regenerative response.
 Typically −55 mV in neurons.
3.3 Non-Decremental Conduction
 APs do not decay with distance.
 Regenerated at each segment of membrane.
3.4 Unidirectional Propagation
 Due to refractory periods:
o Absolute refractory period: Na⁺ channels inactivated, no AP possible.
o Relative refractory period: Stronger stimulus required (K⁺ channels still open).
3.5 Conduction Velocity
 Determined by:
o Axon diameter: Larger → lower resistance → faster conduction.
o Myelination: Saltatory conduction between nodes of Ranvier (up to 100 m/s).
3.6 Stereotyped Shape
 Once initiated, AP has characteristic amplitude, duration, and waveform in a given cell type.

4. Ionic Basis of AP
 Na⁺ current (I_Na): Fast inward, drives depolarization.
 K⁺ current (I_K): Delayed outward, drives repolarization & hyperpolarization.
 Leak currents & pumps: Restore and stabilize RMP.

5. Functional Importance
 Neurons: Long-distance transmission of information.
 Muscle: Triggers contraction (skeletal, cardiac).
 Endocrine cells: Stimulates hormone secretion.
 Synaptic transmission: Presynaptic AP → Ca²⁺ influx → neurotransmitter release.

6. Clinical Relevance
 Local anesthetics (lidocaine, procaine): Block Na⁺ channels → inhibit AP.
 Neurotoxins:
o Tetrodotoxin (TTX) blocks Na⁺ channels.
o Dendrotoxin blocks K⁺ channels.
 Demyelination (MS, Guillain–Barré): Slows conduction → AP failure.
  Electrolyte imbalances:
o Hyperkalemia → depolarization → inactivation of Na⁺ channels → muscle
weakness/arrhythmias.
o Hypokalemia → hyperpolarization → reduced excitability.

7. Quick Recap Table

Property Feature

Threshold Minimum depolarization to trigger AP (~ −55 mV)

All-or-none AP either fires fully or not at all

Amplitude Stereotyped, independent of stimulus strength

Conduction Active, regenerative, non-decremental

Directionality Unidirectional (refractory periods)

Conduction velocity Faster with larger axons & myelination

Na⁺ influx → depolarization; K⁺ efflux →

Ionic basis
repolarization

Key Concept:
An action potential is a self-regenerating, all-or-none electrical event driven by sequential activation of
Na⁺ and K⁺ channels, ensuring reliable, long-distance signaling in excitable cells.