Sequence
of Conductance Changes Underlying the Nerve Action Potential
Some initial depolarization (e.g., a synaptic potential) will begin to open the
Na+ channels. The increase in the Na+ influx leads to a
further depolarization.
Figure 2.6
A positive feedback
cycle rapidly moves the membrane potential toward its peak value, which
is close but not equal to the Na+ equilibrium potential. Two
processes which contribute to repolarization at the peak of the action potential
are then engaged. First, the Na+
conductance starts to decline due to inactivation. As the Na+
conductance decreases, another feedback cycle is initiated, but this one
is a downward cycle. Sodium conductance decreases, the membrane potential
begins to repolarize, and the Na+ channels that are open and
not yet inactivated close. Second, the
K+ conductance increases. Initially, there is very little change
in the K+ conductance because these channels are slow to open,
but by the peak of the action potential, the K+ conductance begins
to increase significantly and a second force contributes to repolarization.
As the result of these two forces, the membrane potential rapidly returns
to the resting potential. At the time it reaches -60 mV, the Na+
conductance has returned to its initial value. Nevertheless, the membrane
potential becomes more negative (the undershoot or the hyperpolarizing afterpotential).
The key to understanding the hyperpolarizing afterpotential is in the slowness
of the K+ channels. Just as the K+ channels are slow to
open, they are also slow to close. Once the membrane potential starts to repolarize,
the K+ channels begin to close because they sense the voltage. However,
even though the membrane potential has returned to -60 mV, some of the voltage-dependent
K+ channels remain open. Thus, the membrane potential will be more
negative than it was initially. Eventually, these K+ channels close,
and the membrane potential returns to -60 mV.
Why does the cell go through these elaborate mechanisms to generate an action
potential with a short duration? Recall how information is coded in the nervous
system. If the action potential was about one msec in duration, the frequency
of action potentials could change from once a second to a thousand a second.
Therefore, short action potentials provide the nerve cell with the potential
for a large dynamic range of signaling.
Pharmacology of the Voltage-Dependent Membrane Channels
Figure 2.7
Some chemical agents can selectively block voltage-dependent membrane channels. Tetrodotoxin
(TTX), which comes from the Japanese puffer fish, blocks the voltage-dependent
changes in Na+ permeability, but has no effect on the voltage-dependent
changes in K+ permeability. This observation indicates that the
Na+ and K+ channels are unique; one of these can be
selectively blocked and not affect the other. Another agent, tetraethylammonia
(TEA), has no effect on the voltage-dependent changes in Na+
permeability, but it completely abolishes the voltage-dependent changes
in K+ permeability.
Figure 2.8
Use these two agents (TTX and TEA) to test your understanding of the ionic
mechanisms of the action potential. What effect would treating an axon with
TTX have on an action potential? An action potential would not occur because
an action potential in an axon cannot be initiated without voltage-dependent
Na+ channels. How would TEA affect the action potential? It would
be longer and would not have an undershoot.
Figure 2.9
In the presence of TEA the initial phase of the action potential
is identical, but note that it is much longer and does not have an after-hyperpolarization.
There is a repolarization phase, but now the repolarization is due to the
process of Na+ inactivation alone. Note that in the presence
of TEA, there is no change in the resting potential. The channels in the
membrane that endow the cell with the resting potential are different from
the ones that are opened by voltage. They are not blocked by TEA. TEA only
affects the voltage-dependent changes in K+ permeability.
