Generation and Conduction of Action Potentials

Lecture 12, BB, Chap. 7, Pgs. 179-185, 206-211

I. Introduction A. action potential characteristics

1. 2. 3. 4. restricted to excitable cells (neurons, muscles, some glands) rapid, stereotyped, reversal of membrane potential propagated non-decrementally basis of nerve signals, some endocrine secretion and EC coupling

II. Local Potential (sub-threshold response) A. resting potential altered by current injection 1. hyperpolarizing current 2 depolarizing current B. local potential 1. change in Vm in response to a current injection 2. local potential amplitude stimulus strength (intensity) 3. also termed graded potential

3. amplitude 1/ recording distance from stimulus (reason for the term "local potential)

III. Action Potential A. threshold 1. minimal effective intensity 2. superthreshold stimulation elicits identical response B. character 1. stereotyped, reversal of Vm 2. amplitude independent of stimulus strength (all or none response)

3. non-decremental conduction

C.

ionic mechanism of action potential 1. resting PD described by GHK equation 2. action potential result of phasic changes in gNa & gK 3. sodium conductance (gNa) a. threshold stimulation gNa b. iNa (influx) result of both chemical and potential gradients c. iNa Vm (depolarization) d. Na channel inactivated gNa ( iNa)

4. potassium conductance (gK) a. threshold stimulation gK (gradual) b. peak gK follows Na inactivation c. K efflux down [ ] gradient d. iK Vm (repolarization) e. gK hyperpolarization (afterpotential)

IV.

Ion Channels

A. conductance regulated by membrane channels 1. channels are ion specific 2. may be voltage, ligand or mechanically gated

structure of membrane channels 1. voltage gated ion channels molecularly similar a. composed of four similar multipass protein domains b. each domain has 6 transmembrane helices 2. extracellular and intracellular loops a. act as gates b. internal loops confer geometry enabling specificity

B. selective blocking agents 1. antagonists selectively block channels 2. may be utilized to characterize ionic fluxes during AP a. tetraethylammonium (TEA) voltage-gated K channel antagonist b. tetrodotoxin (TTX) voltage-gated Na channel antagonist

V. Action Potential Properties A. voltage inactivation 1. depolarize membrane and induce action potential a. reduces amplitude of action potential b. reduces dVm/dt of action potential c. due to reduced "Na driving force" 2. depolarizing membrane beyond threshold results in voltage inactivation

+ 30 O - 3O - 6O - 9O

Time (mV)

mechanism = inactivation of voltage gated sodium channels

B.

refractory periods 1. absolute refractory period a. period immediately following AP b. second AP cannot be induced 2. relative refractory period a. period following absolute refractory period b. limited excitability, superthreshold stimulation required to induce AP 3. mechanism a. voltage gated Na channels inactivated at peak of gNa b. "gates" must be reset for complete excitability

C. accommodation
1. slow depolarization-suprathreshold stimulation is required to produce an AP (b, c, d below) 2. very slow depolarization- no AP possible 3. mechanism a. in slow depolarization some Na channels are being activated, while others are recovering. (b, c and d limited # channels less GNa)

b. voltage inactivation - (e)

VI. conduction (propagation) of action potential

A. bidirectional currents loop to adjacent segments 1. adjacent segments depolarize to threshold 2. new action potential elicited - no loss of amplitude

B. myelination 1. during development, some neural processes wrapped by glial cells 2. results in multilayer myelin sheath with intervening gaps (nodes of Ranvier)

3. myelination enables rapid conduction a. in mylinated axons, AP leaps from node to node b. increases conduction velocity dramatically c. termed saltatory conduction

C. other characteristics of conducted AP 1. velocity fiber diameter 2. neural information coded by frequency, track, but not amplitude

2005 Elsevier