152
Chapter 6
potential, it is
voltage-gated channels
that give a membrane the
ability to undergo action potentials. There are dozens of differ-
ent types of voltage-gated ion channels, varying by which ion
they conduct (e.g., sodium, potassium, calcium, or chloride) and
in how they behave as the membrane voltage changes. For now,
we will focus on the particular types of sodium and potassium
channels that mediate most neuronal action potentials.
Figure 6–18
summarizes the relevant characteristics of
these channels. Sodium and potassium channels are similar
in having sequences of charged amino acid residues in their
structure that make the channels reversibly change shape in
response to changes in membrane voltage. When the mem-
brane is at negative potentials (for example, at the resting
membrane potential) both types of channels tend to close,
whereas membrane depolarization tends to open them. Two
key differences, however, allow these channels to play differ-
ent roles in the production of action potentials. First, sodium
channels are much faster to respond to changes in membrane
voltage. When an area of a membrane is suddenly depolarized,
local sodium channels open well before the potassium chan-
nels do, and if the membrane is then repolarized to negative
voltages, the potassium channels are slower to close. The sec-
ond key difference is that sodium channels have an extra fea-
ture in their cytosolic region, known as an
inactivation gate.
This structure, sometimes visualized as a “ball-and-chain,”
limits the fl ux of sodium ions by blocking the channel shortly
after depolarization opens it. When the membrane repolar-
izes, the channel closes, forcing the inactivation gate back out
of the pore and allowing the channel to return to the closed
state with no sodium fl ux occurring. Integrating these chan-
nel properties with the basic principles governing membrane
potentials, we can now explain how action potentials occur.
Action Potential Mechanism
In our previous coverage of resting membrane potential
and graded potentials, we saw that the membrane potential
depends upon the concentration gradients and membrane per-
meabilities of different ions, particularly sodium and potas-
sium. This is true of the action potential as well. During an
action potential, transient changes in membrane permeability
allow sodium and potassium ions to move down their concen-
tration gradients.
Figure 6–19
illustrates the steps that occur
during an action potential.
In step 1 of the fi gure, the resting membrane potential
is close to the potassium equilibrium potential because there
are more open potassium channels than sodium channels.
Note that these leak channels are distinct from the voltage-
gated channels just described. An action potential begins with
a depolarizing stimulus; for example, when a neurotransmitter
binds to a specifi c ion channel and allows sodium to enter the
cell (review Figure 6–15). This initial depolarization stimu-
lates the opening of some voltage-gated sodium channels,
and further entry of sodium through those channels adds
to the local membrane depolarization. When the membrane
reaches a critical
threshold potential
(step 2), depolarization
becomes a
positive feedback
loop. Sodium entry causes depo-
larization, which opens more voltage-gated sodium channels,
which causes more depolarization, and so on. This process
is represented as a large upstroke of the membrane poten-
tial (step 3), and it overshoots so that the membrane actually
becomes positive on the inside and negative on the outside.
In this phase, the membrane approaches, but does not quite
reach, the sodium equilibrium potential (+60 mV).
As the membrane potential approaches its peak value
(step 4), the sodium permeability abruptly declines as inacti-
vation gates break the cycle of positive feedback by blocking
the open sodium channels. Meanwhile, the depolarized state
of the membrane has begun to open the relatively sluggish
voltage-gated potassium channels, and the resulting elevated
potassium fl ux out of the cell rapidly repolarizes the membrane
toward its resting value (step 5). The return of the membrane
to a negative potential causes voltage-gated sodium chan-
nels to go from their inactivated state back to the closed state
(without opening, as described earlier), and potassium chan-
nels to also return to the closed state. Because voltage-gated
potassium channels close relatively slowly, immediately after
an action potential there is a period when potassium perme-
ability remains above resting levels, and the membrane is
transiently hyperpolarized toward the potassium equilibrium
potential (step 6). This portion of the action potential is known
as the
after-hyperpolarization.
Once the voltage-gated potas-
sium channels fi nally close, however, the resting membrane
potential is restored (step 7). Thus, while voltage-gated sodium
channels operate in a positive feedback mode at the beginning
of an action potential, voltage-gated potassium channels bring
the action potential to an end and induce their own closing
through a
negative feedback
process (
Figure 6–20
).
Figure 6–18
Behavior of voltage-gated sodium and potassium channels.
Depolarization of the membrane causes sodium channels to rapidly
open, then undergo inactivation followed by the opening of
potassium channels. When the membrane repolarizes to negative
voltages, both channels return to the closed state.
Closed
Open
Inactivated
Closed
Open
Repolarization
Depolarization
Na
+
K
+
Channel
Channel states
Sodium
Potassium
Rate
Open and
inactivate
very rapidly
Open and
close slowly
Inactivation
gate
previous page 180 Vander's Human Physiology The Mechanisms of Body Function read online next page 182 Vander's Human Physiology The Mechanisms of Body Function read online Home Toggle text on/off