NROB60 Chapter 44
The Action Potential, In Theory
Depolarization of the cell during the action potential is caused by the influx of sodium ions across the
membrane, and repolarization is caused by the efflux of potassium ions.
Membrane Currents and Conductances
o See Fig. 4.4.
o The membrane of this cell has three types of protein molecules: sodium-potassium pumps, potassium
channels and sodium channels.
o Begin by assuming that both the potassium channels and the sodium channels are closed and that
the membrane potential, V ,mis equal to 0 mV.
Opening the potassium channels only causes the potassium ions to flow out of the cell, down
their concentration gradient, until the inside becomes negatively charged and V m E . k
This movement raises three points:
1) The net movement of potassium ions across the membrane is an electrical current
2) The number of open potassium channels is proportional to an electrical
3) Membrane po+assium current, I , Kill flow only as long as V m E . Khe driving
force on K is defined as the difference between the real membrane potential and
the equilibrium potential, and it can be written asMV -KE .
The Ins and Outs of an Action Potential
o What’s happening with the Na ions concentrated outside the cell?
The membrane potential is so n+gative with respect to the sodium equilibrium potential and
there is a driving force on Na
However there can be no net movement of sodium ions as long as the membrane is
impermeable to Na +
o When the channels are open, however,:
The ionic permeability of the membrane, g Na is high and there is a large driving force pushing
on Na .+
Assuming that th+ membrane permeability is now far greater to sodium than it is to potassium,
this influx of Na depolarizes the neuron until Vmapproaches E , Na mV.
o How could we account for the falling phase of the action potential?
Simply assume that sodium channels quickly close and the potassium channels remain open,
so the dominant membrane ion permeability switches back from Na to K . The potassium
ions would flow out of the cell until the membrane potential again equals EK.
The Action Potential, In Reality
When the membrane is d+polarized to threshold, there is a transient increase in g .Nahe increase in g Na
allows the entry of Na ions, which depolarizes the neuron.
Restoring the negative membrane potential would be further aided by a transient increase in g dKring the
falling phase, allowing K ions to leave the depolarized neuron faster.
The Voltage-Gated Sodium Channel
o Sodium Channel Structure
The voltage-gated sodium channel is created from a single long polypeptide
It has four distinct domains (I-IV) each consisting of six transmembrane alpha helices
(S1 – S6).
The pore is closed at the negative resting membrane potential.
When the membrane is depolarized to threshold, the molecule twists into a configuration that
allows the pass of Na+ through the pore.
The sodium channel is 12 times more permeable to Na than to K . +
The sodium channel is gated by a change in voltage across the membrane o Functional Properties of the Sodium Channel
Changing the membrane potential from -65 to -40 mV causes these channels to pop open
See Fig. 4.9.
These voltage-gated sodium channels have a characteristic pattern of behaviour:
1) They open with little delay
2) They stay open for about 1 msec and then close (inactivate)
3) They cannot be opened again by depolarization until the membrane potential
returns to a negative value near threshold
The fact that single channels do not open until a critical level of membrane
depolarization is reached explains the action potential threshold.
The rapid opening of the channels in response to depolarization explains why the
rising phase of the action potential occurs so quickly
The short time the channels stay open before inactivating partly explains why the
action potential is so brief.
Inactivation of the channels can account for the absolute refractory period
Single amino acid mutations in the extracellular regions of one sodium channel have been
shown to cause a common inherited disorder in human infants known as generalized epilepsy
with febrile seizures.
Generalized epilepsy with febrile seizures is a channelopathy, a human genetic disease
caused by alterations in the structure and function of ion channels.
o The Effects of Toxins on the Sodium Channel
Tetrodotoxin (TTX) clogs the Na - permeable pore by binding tightly to a specific site on the
outside of the channel.
TTX blocks all sodium-dependent action potentials
Voltage-Gated Potassium Channels
o There are many different types of voltage-gated potassium channels.
o Most of them open when the membrane is depolarized and function to diminish any further
depolarization by giving K ions a path to leave the cell across the membrane
o The channel proteins consist of four separate polypeptide subunits that come together to form a pore
These proteins are sensitive to changes in the electrical field across the membrane
o When the membrane is depolarized, the subunits are believed to twist into shape that allows K ions
to pass through the pore.
Putting the Pieces Together
o The key properties of the action potential can be explained using these terms:
Threshold: membrane potential at which enough voltage-gated sodium channels open so that