Resting Membrane Potential and the Action Potential

Neurophysiology, Lecture 1. This lecture covers the biophysical basis of the resting membrane potential and the mechanism of action potential generation and propagation.

RESTING MEMBRANE POTENTIAL

Neurons at rest maintain a stable transmembrane voltage, the resting membrane potential (RMP), of approximately -70 mV (inside negative relative to outside). This potential arises from two factors: (1) differential distribution of ions across the plasma membrane, and (2) selective membrane permeability.

Ion gradients: maintained by the Na+/K+ ATPase (sodium-potassium pump), which actively transports 3 Na+ out and 2 K+ in per cycle, consuming one ATP. This establishes: high intracellular K+ (~140 mM), low extracellular K+ (~5 mM); high extracellular Na+ (~145 mM), low intracellular Na+ (~12 mM). Large negatively charged proteins are trapped inside the cell (fixed anions).

Resting permeability: at rest, the membrane is much more permeable to K+ than Na+ (through leak K+ channels; K+ permeability ~100x greater than Na+). K+ diffuses out down its concentration gradient, taking positive charge out, leaving behind negative fixed anions — generating a negative interior. This continues until the electrical gradient (pulling K+ back in) balances the concentration gradient (diffusing K+ out) — the equilibrium potential for K+ (EK).

Nernst equation: the equilibrium potential for a single ion: E_ion = (RT/zF) x ln([X]o/[X]i). At body temperature: E_K ~ -90 mV; E_Na ~ +60 mV; E_Cl ~ -65 mV. The RMP (-70 mV) is close to EK (because of high K+ permeability) but not as negative, because there is a small resting Na+ permeability pulling the potential toward +60 mV.

Goldman-Hodgkin-Katz (GHK) equation: the actual membrane potential when multiple ions contribute, weighted by their relative permeabilities: V_m = (RT/F) x ln[(P_K[K]o + P_Na[Na]o + P_Cl[Cl]i) / (P_K[K]i + P_Na[Na]i + P_Cl[Cl]o)].

THE ACTION POTENTIAL

The action potential (AP) is a brief, all-or-none depolarisation that propagates without decrement along the axon. Mechanism (Hodgkin-Huxley model):

1. Threshold: when a depolarising stimulus brings the membrane potential to approximately -55 mV (threshold), voltage-gated Na+ channels open. The threshold is the voltage at which the rate of Na+ entry exceeds the rate of K+ repolarisation — a positive feedback loop (Hodgkin cycle) drives explosive depolarisation.

1. Depolarisation phase: voltage-gated Na+ channels open rapidly (activation gate opens); Na+ floods in (down both concentration and electrical gradients); membrane potential rapidly rises to ~+30 to +40 mV (approaching ENa but not reaching it, because inactivation begins).

1. Repolarisation phase: Na+ channel inactivation gate closes (Na+ channels enter the inactivated state, refractory to re-opening); voltage-gated K+ channels open (more slowly) — K+ exits, restoring negative interior.

1. After-hyperpolarisation (undershoot): K+ channels close slowly; the membrane transiently hyperpolarises beyond the RMP (toward EK ~-90 mV) before returning to -70 mV.

1. Absolute refractory period: during the Na+ channel inactivation (depolarisation + early repolarisation phase), no stimulus of any magnitude can trigger another AP. This enforces one-way propagation (the AP cannot travel backwards into the just-fired segment).

1. Relative refractory period: during after-hyperpolarisation, a suprathreshold stimulus can trigger another AP, but a stronger-than-normal stimulus is required. This limits the maximum firing frequency.

PROPAGATION AND CONDUCTION VELOCITY

After the AP fires at one point, local currents depolarise the adjacent axon membrane to threshold, propagating the AP forward. In unmyelinated axons, this is continuous conduction — slow (0.5-2 m/s). In myelinated axons, saltatory conduction occurs: the AP jumps between nodes of Ranvier (only bare membrane with high Na+ channel density), vastly increasing conduction velocity (up to 70-120 m/s for large myelinated fibres). Conduction velocity is proportional to axon diameter and degree of myelination.

Nerve fibre classification: A-alpha (large, myelinated): proprioception, motor (~70-120 m/s); A-beta: touch, pressure (~30-70 m/s); A-delta (small, lightly myelinated): fast pain, temperature (~5-30 m/s); C fibres (unmyelinated): slow pain, temperature, autonomic (~0.5-2 m/s). Local anaesthetics block voltage-gated Na+ channels; small fibres (C, A-delta) blocked first — explains preferential loss of pain before touch.