MOLECULAR-BIOLOGY OF CALCIUM CHANNELS IN THE CARDIOVASCULAR-SYSTEM

Calcium ions are key intracellular messengers in the cardiovascular sy stem. Calcium homeostasis is regulated by an extracellular cycle, whic h controls the entry and removal of calcium between the cytosol and ex tracellular space, and an intracellular cycle, which controls calcium fluxes between the cytosol and intracellular stores in the sarcoplasmi c reticulum. Several protein families mediate these calcium Fluxes inc luding those that (1) regulate the entry of calcium into the cytosol; (2) recognize calcium within the cytosol; and (3) remove calcium from the cytosol. Intracellular calcium binding proteins (the ''E-F hand'' proteins) recognize the appearance of calcium in the cytosol; in the h eart and vascular smooth muscle, these proteins initiate excitation-co ntraction coupling. Calcium efflux occurs via adenosine triphosphate ( ATP)-dependent calcium pumps and sodium-calcium exchangers, while two families of channels-intracellular release calcium channels and plasma membrane calcium channels-regulate calcium entry into the cytosol. Th e plasma membrane calcium channels, which include the L- and T-type ch annels, are of the greatest clinical interest because they are targets for pharmacologic therapy. T-type calcium channels, which activate co ntraction in vascular smooth muscle but have little or no role in card iac excitation-contraction coupling, appear to be involved in signal t ransduction pathways that promote cell growth and proliferation. Calci um channel blockers that selectively block T-type calcium channels, th erefore, offer a novel approach to cardiovascular drug therapy. (C) 19 97 by Excerpta Medica, Inc.