Ca²⁺ channels in the central nervous system

Abstract

Roles of Ca²⁺ channels in physiological functions of mammalian central synapses were discussed from a system-oriented point of view. In the presynaptic terminals of the mammalian CNS so far studied, synaptic transmission is mediated by the subclass of Ca²⁺ channels designated as the Ntype (α_1B channels) and/or by that designated as the P/Q-type (α_1A channels). In some central synapses such as those between neocortical pyramidal neurons, synaptic transmission is presynaptically suppressed by various transmitter-modulators. Our electrophysiological data indicate that the receptors for amines, glutamate, GABA and adenosine co-exist on individual terminals, and they exert a common modulatory effect on synaptic transmission. Details of the intracellular cascade, i.e., G-protein and Ca²⁺ channel subtypes that are linked in this modulation, remain to be elucidated. Although the direct ‘membrane delimited’ action of G-proteins on Ca²⁺ channels is strongly suggested as a modulatory mechanism by the resemblance to the modulation observed in other neurons, the indirect second messenger pathways, however, may also be involved in the control of Ca²⁺ channels. Postsynaptically located Ca²⁺ channels are considered to play important roles in the regulation of neuronal excitability and synaptic plasticity. Individual dendritic spines apparently serve as a primary unit in an increase in Ca²⁺ level. This compartmentalized increase of Ca²⁺ seems essential for determining plastic changes of the synaptic efficacy in those particular spines. There is ample evidence indicating that the postsynaptic Ca²⁺ channels are involved in this Ca²⁺ transient. In order to understand the physiological significance of Ca²⁺ channels in CNS functions, further elucidation of channel subtypes, intracellular cascades of the modulator actions and characterization of the channel modifications will be essential.