ANTAGONISTS OF NEURONAL CALCIUM CHANNELS - STRUCTURE, FUNCTION, AND THERAPEUTIC IMPLICATIONS

This article reviews the structural and functional diversity of neuron al calcium channels and the therapeutic potential of antagonizing such channels, Through spatial and temporal control of intracellular calci um concentration, voltage-sensitive calcium channels regulate a host o f neuronal processes, including neurotransmitter secretion, electrical activity, cytoskeletal function, cell metabolism and proliferation, a nd gene expression, Several genes elaborate a number of calcium channe l isoforms or subtypes-each tailored to specific roles in neuronal fun ction and possessing distinct biophysical properties, distribution, mo dulation, and pharmacological sensitivity. This diversity has raised t he possibility that subtype-specific antagonists could provide novel t reatments for some neuropathologies, In fact, neuroprotective and anal gesic actions of N-type channel blockers in animals appear to confirm this supposition. These properties prompted human clinical studies eva luating these agents for prevention of neuronal degeneration following ischemic brain trauma and for relief of pain. Future medical applicat ions for these blockers and antagonists of other channels subtypes are discussed.