HUMAN PHYSIOLOGY: Excitability & Action Potentials
Ionic Basis of the Action Potential

IONIC BASIS OF THE ACTION POTENTIAL

A. Mechanism of passive movement of Na+ and K+

1. via ion specific channels, with separate channels for Na+ and K+ and Cl-

2. permeability ("P") of Na+ and K+ channels controlled by one or more gates in the respective channel

a. Na+ channel has two gates, an Activation gate (A) and an Inactivation gate (I)

b. Na+ Activation gate is mainly closed at the membrane resting potential but opens rapidly upon membrane depolarization

c. Na+ Inactivation gate is normally open at the membrane resting potential but closes with delay upon membrane depolarization; reopens slowly following repolarization

d. K+ channel involved in the action potential opens with delay upon depolarization; returns slowly to its resting level following repolarization

Note: The Na+ and K+ channel are termed electrically gated channels

 

3. Summary

  P-Na P-K
DEPOLARIZATTION:
Immediate
Opening of Na channel A gate, leading to large (600x) increase of P-Na No Change
DEPOLARIZATION:
Next
Closing of Na channel I gate, leading to decrease of P-Na below its normal resting level Opening of K channel gate, leading to P-K increase (10x)
REPOLARIZATION
Gradual
Return of P-Na gates to their resting state (capable of another activation) Return of P-K to its resting level (decrease)

B. Permeability Changes During Action Potential

1. Changes on initial depolarization (upstroke of AP)


2. Hodgkin cycle

If depolarization proceeds until the P-Na increase causes

Na influx > K efflux + Cl influx (threshold exceeded)

then depolarization becomes regenerative: Hodgkin Cycle (example of regenerative behavior or positive feedback)

Membrane potential moves toward (but does not reach) E-Na (sodium equilibrium potential)

3. Subsequent event (down stroke of AP)

P-K increase and P-Na decrease causes Vm to return to its resting level approaching E-K

4. Final event (refractory period)

Following repolarization, several msec are required for P-Na to increase and P-K to decrease to their resting levels; until this occurs, the membrane is absolutely or relatively refractory

SUMMARY: In each action potential, a small amount of Na enters the neuron and a small amount of K leaves the neuron

Question: What would be the expected effect of hypokalemia (low blood potassium) on neuron excitability?

C. Role of Active Transport

1. Establishes original Na+ and K+ concentration gradients (energy source)

2. Not directly involved in the action potential

3. Eventually restores intracellular concentrations of Na+ and K+ after the action potential is over (minutes)

Note: In the peripheral nervous system, the normal concentrations of Na+ and K+ are sufficient to sustain a number of action potentials without additional active transport, but without active transport nerve axons eventually will lose their ability to generate action potentials