excitable membranes

excitablemembranes

action potential & propagation

Basic Neuroscience NBL 120 (2007)

ionic basis of APs

action potentials:

faithfully transmit information along the membrane (axon) of excitable cells

allow rapid communication between distant parts of a neuron

action potentials

the action potential is a regenerative electrochemical signal

two distinct voltage-gated ion channels are responsible for action potential generation

the action potential

3 main stages: resting

i.e. RMP

depolarization reversal of

membrane potential

repolarization return of membrane potential

to RMP

relationship between: membrane potential

ion equilibrium potentials

if the membrane becomes more permeable to one ion over other ions then the membrane potential will move towards the equilibrium potential for that ion (basis of AP).

membranepotential (mV)

EK

ENa

RMP

+67

-90-98

ECl

general rule

depolarization

rapid opening of Na-selective channels

entry of Na “down” its electrochemical gradient 1. membrane more permeable to Na than K 2. membrane potential moves towards Ena

3. because ENa is +ve the AP overshoots zero

4. At the peak of the AP Na is the primary ion determining the membrane potential

repolarization

closure (inactivation) of Na-selective channels slower opening of K-selective channels

1. membrane more permeable to K than Na2. membrane potential moves towards EK

the opening and closing of AP Na and K channels are controlled by changes in the membrane potential

voltage-gated ion channels

properties (e.g. time course) of voltage-gated channels are more easily examined using the voltage-clampholds or clamps the membrane constantmovement of ions (current) through the

channels is measured directly

voltage-clamp

relationship between: membrane potential ion equilibrium potentials

artificial manipulation of MP (voltage-clamp) - current will flow in the direction to move the MP towards the equilibrium potential of open ion channel

membranepotential (mV)

EK

ENa

RMP

+67

-90-98

ECl

general rule

voltage-clamp used to rapidly change the membrane potential over the same range as occurs during the AP2 current phases

rapid / transient inward current

slower outward steady current

AP current time course

the inward phase

carried by Na ions

selective agents block the 2 components

2 independent channels

all-or-none AP are not graded potentials

threshold in order for an AP to occur the membrane must be

depolarized beyond a threshold level inward Na overcomes resting outward K movement

electrical stimulation synaptic activation

what triggers an AP?

APs are regenerative

activation of Na channels is cyclical initial depolarizationopening of Na channelsNa entryetc..

accomodation

side-effects of inactivation

disease (e.g. paramyotonia congenita)

action potential review

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membrane capacitance properties

“bulk” solutions in and out are neutralthe transmembrane potential difference

exists within a narrow band just across the membrane capacitor:

separates / stores charge

time constant

changing the membrane voltage takes time charging a capacitor is not instantaneous

inject currentrecord voltage

axon

I

V

m= rmcm

how can AP rise so fast?

mrmcm

how electrical signals propagate

passive decay

length constant

length constant (passive process)

axon / dendritemembrane resistance (rm)

axial, or internal, resistance (ri)

diameter (d)

rm

ri (+ re) =

AP propagation

APs are conducted along excitable cell membranes away from their point of origine.g. down the axon

from cell soma to terminal

depolarization of the membrane during the AP is not restricted

to a single spot

the inward current carried by Na ions during the AP depolarizes adjacent portions of the membrane beyond threshold and the regenerative AP travels (in both directions) along the membrane

local circuits

following a single AP a second AP cannot be generated at the same site for some time (absolute versus relative)Na channels need to recover from inactivationopen K channels oppose inward Na movement

refractory period

local circuit propagation is slow (< 2 m/s) In motorneurons propagation is fast 100 m/s Schwann cell

envelop axons / layer of insulation increase resistance (Rm)(increase length constant) eliminate capacitance(time constant > 0)

Nodes of Ranvier discontinuity in myelin sheath (every few 200+ m)

myelination

saltatory conduction

APs are only generated at Nodes of Ranvier high density of Na / K channels

current flows rapidly between nodes little current leakage between nodes

AP “jumps” down fiber as successive nodal membrane capacitances are discharged

propagation review

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myelination disease

Charcot-Marie tooth disease progressive loss of PNS axons - weakness, atrophy

Node of RanvierSchwann cell

summary

RMP electrochemical gradients Nernst equation

AP initiation role of voltage-sensitive Na and K channels regenerative depolarization threshold and accommodation

passive properties time and length constants capacitance

AP propagation local circuits saltatory conduction