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Section I:
Cellular and Molecular Neurobiology

2. Ionic Mechanisms of Action Potentials
Part 3 of 3

Pumps and Leaks

It is easy to receive the impression that there is a "gush" of Na⁺ that comes into the cell with each action potential. Although, there is some influx of Na⁺, it is minute compared to the intracellular concentration of Na⁺. The influx is insufficient to make any noticeable change in the intracellular concentration of Na⁺. Therefore, the Na⁺ equilibrium potential does not change during or after an action potential. For any individual action potential, the amount of Na⁺ that comes into the cell and the amount of K⁺ that leaves are insignificant and have no effect on the bulk concentrations. However, without some compensatory mechanism, over the long-term (many spikes), Na⁺ influx and K⁺ efflux would begin to alter the concentrations and the resultant Na⁺ and K⁺ equilibrium potentials. The Na⁺-K⁺ pumps in nerve cells provide for the long-term maintenance of these concentration gradients. They keep the intracellular concentrations of K⁺ high and the Na⁺ low, and thereby maintain the Na⁺ equilibrium potential and the K⁺ equilibrium potential. The pumps are necessary for the long-term maintenance of the "batteries" so that resting potentials and action potentials can be supported.

Test Your Knowledge

3. Drug X, when applied to a nerve axon, results in both a gradual decrease in the amplitude of individual action potentials and a depolarization of the resting potential, both of which develop over a period of several hours. The drug is most likely:

⁺

Types of Membrane Channels

So far, two basic classes of channels, voltage-dependent or voltage-gated channels and voltage independent channels, have been considered. Voltage-dependent channels can be further divided based on their permeation properties into voltage-dependent Na⁺ channels and voltage-dependent K⁺ channels. There are also voltage-dependent Ca²⁺ channels (see below). Indeed, there are multiple types of Ca²⁺ channels and about 20 different types of voltage-dependent K⁺ channels. Nevertheless, all these channels are conceptually similar. They are membrane channels that are normally closed and as a result of changes in potential, the channel (pore) is opened. The amino acid sequence of these channels is known in considerable detail and specific amino acid sequences have been related to specific aspects of channel function (e.g., ion selectivity, voltage gating, inactivation). A third major channel class, the transmitter-gated or ligand-gated channels, will be described later.

Absolute and Relative Refractory Periods

The absolute refractory period is a period of time after the initiation of one action potential when it is impossible to initiate a second action potential no matter how much the cell is depolarized. The relative refractory period is a period after one action potential is initiated when it is possible to initiate a second action potential, but only with a greater depolarization than was necessary to initiate the first. The relative refractory period can be understood at least in part by the hyperpolarizing afterpotential. Assume that an initial stimulus depolarized a cell from -60 mV to -45 mV in order to reach threshold and then consider delivering the same 15-mV stimulus sometime during the after-hyperpolarization. The stimulus would again depolarize the cell but the depolarization would be below threshold and insufficient to trigger an action potential. If the stimulus was made larger, however, such that it again was capable of depolarizing the cell to threshold (-45 mV), an action potential could be initiated.

The absolute refractory period can be explained by the dynamics of the process of Na⁺-inactivation, the features of which are illustrated in Figure 2.10. Here, two voltage clamp pulses are delivered. The first pulse produces a voltage-dependent increase in the Na⁺ permeability which then undergoes the process of inactivation. If the two pulses are separated sufficiently in time, the second pulse produces a change in the Na⁺ conductance, which is identical to the first pulse. However, if the second pulse comes soon after the first pulse, then the change in Na⁺ conductance produced by the second pulse is less than that produced by the first. Indeed, if the second pulse occurs immediately after the first pulse, the second pulse produces no change in the Na⁺ conductance. Therefore, when the Na⁺ channels open and spontaneously inactivate, it takes time (several msec) for them to recover from that inactivation. This process of recovery from inactivation underlies the absolute refractory period. During an action potential the Na⁺ channels open and then they become inactivated. Therefore, if a second stimulus is delivered soon after the one that initiated the first spike, there will be few Na⁺ channels available to be opened by the second stimulus because they have been inactivated by the first action potential.

Figure 2.10

Action Potential Laboratory

Click here to go to the interactive Action Potential Laboratory to examine the ways in which the action potential is effected by changes in the Na⁺ conductance, K⁺ conductance and equilibrium potentials for Na⁺ and K⁺.

Action Potential Laboratory

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Neuroscience Online

Pumps and Leaks

Test Your Knowledge

Types of Membrane Channels

Absolute and Relative Refractory Periods

Action Potential Laboratory

Neuroscience
Online