The process of encoding is usually further modulated by the two other types of ion channels in the initial segment that were mentioned earlier—voltage-gated Ca2+ channels and Ca2+-activated K+ channels. They act together to decrease the response of the cell to an unchanging, prolonged stimulation—a process called adaptation. These Ca2+ channels are similar to the Ca2+ channels that mediate the release of neurotransmitter from presynaptic axon terminals; they open when an action potential fires, transiently allowing Ca2+ into the axon cytosol at the initial segment.
The Ca2+-activated K+ channel opens in response to a raised concentration of Ca2+ at the channel’s cytoplasmic face (Figure 11–42). Prolonged, strong depolarizing stimuli will trigger a long train of action potentials, each of which permits a brief influx of Ca2+ through the voltage-gated Ca2+ channels, so that local cytosolic Ca2+ concentration gradually builds up to a level high enough to open the Ca2+-activated K+ channels. Because the resulting increased permeability of the membrane to K+ makes the membrane harder to depolarize, the delay between one action potential and the next is increased. In this way, a neuron that is stimulated continuously for a prolonged period becomes gradually less responsive to the constant stimulus.
Such adaptation, which can also occur by other mechanisms, allows a neuron—indeed, the nervous system generally—to react sensitively to change, even against a high background level of steady stimulation. It is one of the computational strategies that help us, for example, to feel a light touch on the shoulder and yet ignore the constant pressure of our clothing. We discuss adaptation as a general feature in cell signaling processes in more detail in Chapter 15.
Other neurons do different computations, reacting to their synaptic inputs in myriad ways, reflecting the different assortments of ion channels in their membrane. There are several hundred genes that code for ion channels in the human genome, with over 150 encoding voltage-gated channels alone. Further complexity is introduced by alternative splicing of RNA transcripts and assembling channel subunits in different combinations. Moreover, ion channels are selectively
Figure 11–41 The magnitude of the combined postsynaptic potential (PSP) is reflected in the frequency of firing of action potentials. The mix of excitatory and inhibitory PSPs produces a combined PSP at the initial segment. A comparison of (A) and (B) shows how the firing frequency of an axon increases with an increase in the combined PSP, while (C) summarizes the general relationship.
localized to different sites in the plasma membrane of a neuron. Some K+ and Ca2+ channels are concentrated in the dendrites and participate in processing the input that a neuron receives. As we have seen, other ion channels are located at the axon’s initial segment, where they control action potential firing; and some ligand-gated channels are distributed over the cell body and, depending on their ligand occupancy, modulate the cell’s general sensitivity to synaptic inputs. The multiplicity of ion channels and their locations evidently allows each of the many types of neurons to tune the electrical behavior to the particular tasks they perform.
One of the crucial properties of the nervous system is its ability to learn and remember. This property depends in part on the ability of individual synapses to strengthen or weaken depending on their use—a process called synaptic plasticity. We end this chapter by considering a remarkable type of ion channel that has a special role in some forms of synaptic plasticity. It is located at many excitatory synapses in the central nervous system, where it is gated by both voltage and the excitatory neurotransmitter glutamate. It is also the site of action of the psychoactive drug phencyclidine, or angel dust.
Long-Term Potentiation (LTP) in the Mammalian Hippocampus Depends on Ca2+ Entry Through NMDA-Receptor Channels