The intensity of stimulation that a neuron receives is encoded by that neuron into action potential frequency for long-distance transmission. The encoding takes place at a specialized region of the axonal membrane known as the initial segment, or axon hillock, at the junction of the axon and the cell body (see Figure 11–40). This membrane is rich in voltage-gated Na+ channels; but it also contains at least four other classes of ion channels—three selective for K+ and one selective for Ca2+—all of which contribute to the axon hillock’s encoding function. The three varieties of K+ channels have different properties; we shall refer to them as delayed, rapidly inactivating, and Ca2+-activated K+ channels.
To understand the need for multiple types of channels, consider first what would happen if the only voltage-gated ion channels present in the nerve cell were the Na+ channels. Below a certain threshold level of synaptic stimulation, the depolarization of the initial-segment membrane would be insufficient to trigger an action potential. With gradually increasing stimulation, the threshold would be crossed, the Na+ channels would open, and an action potential would fire. The action potential would be terminated by inactivation of the Na+ channels. Before another action potential could fire, these channels would have to recover from their inactivation. But that would require a return of the membrane voltage to a very negative value, which would not occur as long as the strong depolarizing stimulus (from PSPs) was maintained. An additional channel type is needed, therefore, to repolarize the membrane after each action potential to prepare the cell to fire again.
The delayed K+ channels perform this task, as discussed previously in relation to the propagation of the action potential (see Figure 11–31). They are voltage-gated, but because of their slower kinetics they open only during the falling phase of the action potential, when the Na+ channels are inactive. Their opening permits an efflux of K+ that drives the membrane back toward the K+ equilibrium potential, which is so negative that the Na+ channels rapidly recover from their inactivated state. Repolarization of the membrane also closes the delayed K+ channels. The initial segment is now reset so that the depolarizing stimulus from
Figure 11–40 a motor neuron in the spinal cord. (A) Many thousands of nerve terminals synapse on the cell body and dendrites. These deliver signals from other parts of the organism to control the firing of action potentials along the single axon of this large cell. (B) Fluorescence micrograph showing a nerve cell body and its dendrites stained with a fluorescent antibody that recognizes a cytoskeletal protein (green) that is not present in axons. Thousands of axon terminals (red) from other nerve cells (not visible) make synapses on the cell body and dendrites; the terminals are stained with a fluorescent antibody that recognizes a protein in synaptic vesicles. (B, courtesy of Olaf Mundigl and Pietro de Camilli.) frequency of fring(action potentials per second) magnitude of combined PSP synaptic inputs can fire another action potential. In this way, sustained stimulation of the dendrites and cell body leads to repetitive firing of the axon.
Repetitive firing in itself, however, is not enough. The frequency of firing has to reflect the intensity of stimulation, and a simple system of Na+ channels and delayed K+ channels is inadequate for this purpose. Below a certain threshold level of steady stimulation, the cell will not fire at all; above that threshold level, it will abruptly begin to fire at a relatively rapid rate. The rapidly inactivating K+ channels solve the problem. These, too, are voltage-gated and open when the membrane is depolarized, but their specific voltage sensitivity and kinetics of inactivation are such that they act to reduce the rate of firing at levels of stimulation that are only just above the threshold required for firing. Thus, they remove the discontinuity in the relationship between the firing rate and the intensity of stimulation. The result is a firing rate that is proportional to the strength of the depolarizing stimulus over a very broad range (Figure 11–41).