Repolarization

What causes Em to return to rest again following the regenerative depolarization during an action potential? There are two important factors: (1) the depolarization-induced increase in pNa is transient; and (2) there is a delayed, voltage-dependent increase in pK. These will be discussed in turn below.

The effect of depolarization on the voltage-dependent sodium channels is twofold. These effects can be summarized by the diagram in Figure 6-6, which illustrates the behavior of a single voltage-sensitive sodium channel in response to a depolarization. The channel acts as though the flow of Na+ is controlled by two independent gates. One gate, called the m gate, is closed when Em is equal to or more negative than the usual resting potential. This gate thus prevents Na+ from entering the channel at the resting potential. The other gate, called the h gate, is open at the usual resting Em. Both gates respond to depolarization, but with different speeds and in opposite directions. The m gate opens rapidly in response to depolarization; the h gate closes in response to depolarization, but does so slowly. Thus, immediately after a depolarization, the m gate is open, allowing Na+ to enter the cell, but the h gate has not had time to respond to the depolarization and is thus still open. A little while later (about a millisecond or two), the m gate is still open, but the h gate has responded by closing, and the channel is again closed. The result of this behavior is that pNa first increases in response to a depolarization, then declines again even if the depolarization were maintained in some way. This delayed decline in sodium permeability upon depolarization is called sodium channel inactiva-tion. As shown in Figure 6-4, this return of pNa to its resting level would alone be sufficient to bring Em back to rest.

In addition to the voltage-sensitive sodium channels, there are voltage-sensitive potassium channels in the membranes of excitable cells. These channels are also closed at the normal resting membrane potential. Like the sodium channel m gates, the gates on the potassium channels open upon depolarization, so that the channel begins to conduct K+ when the membrane potential is reduced. However, the gates of these potassium channels, which are called n gates, respond slowly to depolarization, so that pK increases with a delay following a depolarization. The characteristic behavior of a single voltage-sensitive potassium channel is shown in Figure 6-7. Unlike the sodium channel, there is no gate on the potassium channel that closes upon depolarization; the channel remains open as long as the depolarization is maintained and closes only when membrane potential returns to its normal resting value.

These voltage-sensitive potassium channels respond to the depolarizing phase of the action potential and open at about the time sodium permeability returns to its normal low value as h gates close. Therefore, the repolarizing phase of the action potential is produced by the simultaneous decline of pNa to its resting level and increase of pK to a higher than normal level. Note that during this time, pNa/pK is actually smaller than its usual resting value. This explains the undershoot of membrane potential below its resting value at the

Plasma membrane

Outside
Immediately after depolarization (Em = -50 mV) m gate open h gate open

Outside

Outside

5 ms after depolarization (£m = -50 mV) m gate open h gate closed h gate

Figure 6-6 A schematic representation of the behavior of a single voltage-sensitive sodium channel in the plasma membrane of a neuron. (a) The state of the channel at the normal resting membrane potential. (b) Upon depolarization, the m gate opens rapidly and sodium ions are free to move through the channel. (c) After a brief delay, the h gate closes, returning the channel to a nonconducting state.

5 ms after depolarization (£m = -50 mV) m gate open h gate closed h gate

Figure 6-6 A schematic representation of the behavior of a single voltage-sensitive sodium channel in the plasma membrane of a neuron. (a) The state of the channel at the normal resting membrane potential. (b) Upon depolarization, the m gate opens rapidly and sodium ions are free to move through the channel. (c) After a brief delay, the h gate closes, returning the channel to a nonconducting state.

Plasma membrane

Figure 6-7 The behavior of a single voltage-sensitive potassium channel in the plasma membrane of a neuron. (a) At the normal resting membrane potential, the channel is closed. (b) Immediately after a depolarization, the channel remains closed. (c) After a delay, the n gate opens, allowing potassium ions to cross the membrane through the channel. The channel remains open as long as depolarization is maintained.

Figure 6-7 The behavior of a single voltage-sensitive potassium channel in the plasma membrane of a neuron. (a) At the normal resting membrane potential, the channel is closed. (b) Immediately after a depolarization, the channel remains closed. (c) After a delay, the n gate opens, allowing potassium ions to cross the membrane through the channel. The channel remains open as long as depolarization is maintained.

Table 6-1 Summary of responses of voltage-sensitive sodium and potassium channels to depolarization.

Type of Response to Speed of channel Gate depolarization response

Sodium m gate Opens Fast

Sodium h gate Closes Slow

Potassium n gate Opens Slow end of an action potential: Em approaches closer to EK because pK is still higher than usual while pNa has returned to its resting state. Membrane potential returns to rest as the slow n gates have time to respond to the repolarization by closing and returning pK to its normal value.

The sequence of changes during an action potential is summarized in Figure 6-8, and characteristics of the various gates are summarized in Table 6-1. An action potential would be generated in the sensory neuron of the patellar reflex in the following way. Stretch of the muscle induces depolarization of the specialized sensory endings of the sensory neuron (probably by increasing the relative sodium permeability). This depolarization causes the m gates of voltage-sensitive sodium channels in the neuron membrane to open, setting in motion a regenerative increase in pNa, which drives Em up near ENa. With a delay, h gates respond to the depolarization by closing and potassium-channel n gates respond by opening. The combination of these delayed gating events drives Em back down near EK and actually below the usual resting Em. Again with a delay, the repolarization causes the h gates to open and the n gates to close, and the membrane returns to its resting state, ready to respond to any new depolarizing stimulus.

The scheme for the ionic changes underlying the nerve action potential was worked out in a series of elegant electrical experiments by A. L. Hodgkin and A. F. Huxley ofCambridge University. Chapter 7 describes those experiments and presents a quantitative version of the scheme shown in Figure 6-8.

0 0

Post a comment