Calcium channels in cerebral arteries

Abstract

Electrophysiological evidence shows the existence of voltage-operated Ca 2+ channels of the L- and, in some cases, T- and B-, type in the smooth muscle cells of major cerebral arteries and arterioles. Current intensity through L-type Ca 2+ channels is higher in cerebral than in peripheral arteries, which points to a greater dependence on extracellular Ca 2+ of contractile responses in cerebral arteries. The increase in cytosolic Ca 2+ concentration is the key event leading both to maintenance of basal cerebrovascular tone and to contraction of cerebral arteries in response to depolarization and agonist-receptor interaction. Such an increase results from increased transmembrane influx of Ca 2+ through L-type Ca 2+ channels, as well as from the release of Ca 2+ from intracellular Ca 2+ stores. Ca 2+ entry modulators (dihydropyridines, phenylalkylamines, benzothiazepines, and diphenylpiperazines) bind to allosterically coupled sites in the Ca 2+ channel, thus inhibiting (Ca 2+ entry blockers) or stimulating (Ca 2+ entry activators) Ca 2+ influx and, therefore, contractile responses of the cerebral arteries. In vivo, Ca 2+ entry blockers increase pial vascular caliber and cerebral blood flow by their direct action on the cerebroarterial wall. However, such an action also takes place on several peripheral vascular beds, which leads to hypotension. Therefore, the brain cannot be considered a “privileged” organ when the vasodilatatory action of Ca 2+ entry blockers is considered. Since increased cytosolic Ca 2+ concentration (and, therefore, activation of Ca 2+ channels) plays a crucial role in the pathogenesis of ischemic brain damage (e.g., acute stroke and subarachnoid hemorrhage), Ca 2+ entry blockers could be useful cytoprotective drugs. However, with the exception of nimodipine in the management of subarachnoid hemorrhage, clinical trials have yielded results that are not so promising as one could expect from those obtained in experimental research.