5.

Ac&on Poten&als

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Outline
Basic experimental ndings
cri&cal experimental observa&ons of ac&on poten&als
the voltage-clamp experimental setup

Elements of the HH model

mathema&cal descrip&on of the selec&ve ow of ions
across excitable membrane.
integrates the ionic current equa&ons into the overall
model for membrane currents and poten&als

Extensions to the HH model

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In a nutshell
The ac&on poten&al cycle
consists of a rapid membrane
depolariza,on (i.e., an increase
in transmembrane poten&al)
followed by a slower recovery to
res,ng condi&ons.
Once an ac&on poten&al is
ini&ated at one site on a
membrane, it ini&ates ac&on
poten&als at adjacent sites, thus
leading to a propaga,on of the
ac&on poten&al throughout the
remaining membrane.

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Observa&ons
Concurrent with the s&mulus current,
Vm shows a small direct response.
A much larger and more energe&c
second deec&on occurs AP
AP is a consequence of the s&mulus,
but is generated by the charged energy
stored in the concentra,on
dierences that exist across the
excitable membrane
This stored energy allows rst the ow
of Na+ ions (Vm increase) and then the
ow of K+ ions (Vm decrease).
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Experimental Setup
Individual bers can be teased
out and a single ber iden&ed
at its proximal and distal end.
AP main characteris,cs:
Threshold response
All or None nature
Fiber diameter (conduc&on
without decrement)
Latency (refractory period)
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From Aidley DJ. 1978.

Recording Setup

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Changing the membrane Poten&al

Depolariza&on

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Changing the membrane current

Hyper polariza&on

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AP characteris&cs 1: Threshold response

The AP results from an
increase in ionic
conductance of the
membrane.
Historic recording (1939)
by Kenneth Cole and
Howard Cur&s:
Oscilloscope record of an
AP superimposed on a
simultaneous record of
membrane conductance.
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AP Characteris&cs 2: All or None

The size and shape of
an ac&on poten&al
ini&ated by a large
depolarizing current
is the same as that of
an ac&on poten&al
evoked by a current
that just surpasses
the threshold.
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AP Characteris&cs 3: Conduc&on
AP is conducted without
decrement.
It has a self-regenera&ve
feature that keeps the
amplitude constant, even
when it is conducted over
great distances

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AP Characteris&cs 4: Latency
AP is followed by a refractory
period.
For a brief &me ader an AP is
generated, the cells ability to
re a second ac&on poten&al
is suppressed.
The refractory period limits
the frequency at which a
nerve can re ac&on
poten&als, and thus limits the
informa&on-carrying capacity
of the axon
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But what mechanisms are responsible for

regula&ng the changes in the Na+ and K+
permeabili&es of the membrane?

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The Voltage Clamp: Why?

Need to interrupt the posi&ve feedback cycle
resul&ng from con&nuous inux of Na+ ions
when they open upon depolariza&on

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The Voltage Clamp: How does it work?

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Eects of small and

large depolariza&on
under VC

tetrodotoxin (TTX), a Na+ current blocker

tetraethylammonium (TEA), a K+ current blocker

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Magnitude AND Polarity of Na+ and K+

membrane currents vary with the amplitude of membrane
depolariza&on

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Conductance measurements using VC

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The Ac&on Poten&al

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Analysis of the dynamics of ionic

currents during VC

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HH Model Assump&ons
Early current is Na+ current alone:

IK = 0 for 0 t T/3, where T is the &me of peak inward

current

Outside Na+ aects INa

for two experiments at the same voltage clamp, but

dierent [Na+]o, only the driving force changes, going from
(Vm ENa) to (Vm ENa) such that INa(t)/INa(t) = constant A

Ionic Independence

IK(t) = IK (t). Since [K+]i and [K+]o are unchanged, the K+

current (for the same voltage clamp) in normal seawater is
the same as in 10% sodium seawateri.e., independent of
A, the ra&o of Na+ currents.

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 Lets examine the early por&on of the total

current for a normal voltage clamp Im(t) and
the low-sodium current Im(t).
Assuming no K+ contribu&on, the ra&o
Im(t)/Im (t) gives the value of A
Advance &me step, so that at any t = t1

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 Using independence assump&ons,

Elimina&ng either IK or INa to obtain the

desired value of Na+ and K+ ion components
at t1

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What are these current values good

for?

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HH model conductance equa&ons

(1)

constant during a voltage clamp!

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(2)

Experimentally measured
Conductance dynamics over &me

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Now we need equa&ons describing the

temporal varia&on for n, m and h

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HH Model for K+
The potassium conductance gK(t, vm)

Assuming n to obey rst-order kine&cs,

Solving
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conductance
when all
channels are
open

 we can re-write

Op&mal t of this rate equa&on to data is obtained

by adjus&ng n and n. The rate constants become
These rates are found by solving, simultaneously,
the equa&ons before to get

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 treat the resul&ng set n(vmi), n(vmi) as

samples of analy&c func&ons (vm), (vm)
Hodgkin and Huxley, through curve yng,
described these (for K+) to be
vm is in mV
, are in msec1
vm = Vm Vrest

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HH model for Na+

Same for Na+
(5)

We may interpret m3h as the probability that

a sodium channel is open.
Hence, for a large popula&on, m3h is the
frac&on of the all-sodium channels that are
open.
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 As with K+, we can also assume that for the sodium protein
structure to yield an open pore we require conforma&onal
changes in which each of four subunits are in an open
posi&on.
For Na+ three subunits have m as the probability of their
being open, while the fourth is described by the probability
h of being open
(3)

(4)

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 The value of can be found from the measured

voltage clamp data using the asympto&cally largest
value of conductance obtained all-sodium
channels are open.
Thus, if there are Nna channels per unit area and each
has a conductance of Na, then

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 Equa&ons (3) and (4) can be solved under

voltage clamp condi&ons (where and are
constants for each clamped value of vm),

asympto&c
condi&ons of
m and h with
increasing
&me

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 For vm > 30 mV an ac&on

poten&al is certain to be
elicited, and in the steady state
that follows, gNa 0, so m0 0
since m(t) is an increasing
func&on, we deduce that h 0
Using equa&on (5) for Na+
conductance together with the
asympto&c condi&ons of m and
h with increasing &me

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 For each voltage clamp vm and corresponding

experimental curve gNa(t, vm), the values of m,
h, m can be chosen so that it best ts the
data

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Time constants observed experimentally

Using experimental data, HH t

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The leakage current

(6)

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 The cri&cal ques&on is whether the equa&ons

accurately predict the results for non-voltage-
clamp situa&ons, i.e., are the equa&ons correct
for naturally occurring ac&on poten&als?
The answer is yes. This predic&ve power is why
the HH formula&on came to be considered a true
formula&on of how the membrane responds to
many dierent situa&ons and s&muli.
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Sum of currents

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 the capaci&ve current IC is equal to CmdVm/dt,

thus introducing &me explicitly.
Further, the &me deriva&ve dVm/dt can be
approximated as

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Similarly for ga&ng variables

In the simula&on of membrane ac&on
poten&als using HodgkinHuxley formalism,
the state variables are vm, n, m, and h.
This means that all the other &me-varying
quan&&es, such as IK and INa, can be found
from the values of the state variables

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Simula&ng the model

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Ionic currents

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The refractory period


Absolute refractory period
followed by a rela&ve
refractory period
Refractoriness can be
understood mainly by the
behavior of the inac&va&ng
parameter h.

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Return to rest

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