A Novel Ca 2+ Channel in Vascular Smooth Muscle?

Contraction of vascular smooth muscle cells (VSMCs) requires an increase in [Ca2+]i. This increase can occur via Ca2+ release from the sarcoplasmic reticulum or by influx of Ca2+ from the extracellular space through voltage-dependent Ca2+ channels (VDCCs) or receptor operated nonselective cation channels.1 A number of studies using dissociated or cultured VSMCs with origins from a range of vascular beds have demonstrated, using electrophysiological and molecular techniques, that a major contribution to Ca2+ influx in response to membrane depolarization and/or vasoactive agents is mediated via VDCCs. Two types of VDCCs have been recorded in VSMCs: L- and T-type. The L-type Ca2+ current is classified as high voltage activated (HVA) because it activates at membrane potentials at or more positive than −40 mV. The L-type class of VDCCs has a distinct pharmacology. L-type VDCCs are dihydropyridine (DHP) sensitive, and molecular cloning has confirmed that these channels contain unique domains on the pore-forming α subunit that confer this sensitivity. Because the L-type VDCC is a major contributor to vascular tone, its unique pharmacology has been exploited to treat cardiovascular disorders such as hypertension.1 However, the ubiquitous expression of L-type Ca2+ channels in many cell types causes undesirable side effects when DHPs are clinically used.Fewer published studies have shown that T-type Ca2+ current exists in smooth muscle cells.2 3 4 5 6 7 Unlike the HVA channels, electrophysiological data show that T-type Ca2+ current is DHP insensitive and activates at more negative …