Vascular Smooth Muscle Calcium Channels

Abstract

Voltage-gated Ca2+ channels of the plasma membrane open in response to changes in cell membrane potential, providing an important pathway for regulated entry of extracellular Ca2+ ions. Ca2+ channels comprise a family of structurally related proteins displaying tissue- and stage-specific expression. They are classified as either high voltage-activated (HVA) or low voltage-activated (LVA) and can be subdivided further based on their pharmacological properties. HVA channels include L-, N-, P-/Q-, and R-types, and LVA channels are designated as T-type. Members of each subtype have been identified by molecular cloning, facilitating studies of their biophysical properties, relative distribution, and contribution to Ca2+-dependent cellular functions. In recent years, it has become increasingly clear that in most, if not all, cases, more than one class of voltage-dependent Ca2+ channel are expressed in a given cell type. The functional relevance of different Ca2+ channels within a cell, however, remains unclear. In contractile cells, voltage-gated Ca2+ channels are particularly important because influx of extracellular Ca2+ is essential for muscle contraction and maintenance of tension. Ca2+ channels have received a great deal of attention in vascular smooth muscle (VSM), where calcium influx affects arterial vasoconstriction and vasorelaxation, and ultimately influences systemic blood pressure. Resistance arteries are an important site of blood pressure regulation. These arteries normally exist in a relatively contracted state and can undergo either dilation or constriction, depending on the contractile state of the arterial VSM. Ca2+ channel activity is a key determinant of VSM contractile state, and L-type Ca2+ channels are the classic target of calcium channel blockers (CCBs) widely prescribed as antihypertensive drugs. Therefore, a wealth of information has been published comparing different calcium antagonists, or CCBs, and their inhibitory affects on L-type calcium currents and vasoconstriction. It is important to …