Metabotropic Ca2+ channel-induced calcium release in vascular smooth muscle

Contraction of vascular smooth muscle cells (VSMCs) depends on the rise of cytosolic [Ca2+] owing to either Ca2+ influx through voltage-gated Ca2+ channels of the plasmalemma or to receptor-mediated Ca2+ release from the sarcoplasmic reticulum (SR). Although the ionotropic role of L-type Ca2+ channels is well known, we review here data suggesting a new role of these channels in arterial myocytes. After sensing membrane depolarization Ca2+ channels activate G proteins and the phospholipase C/inositol 1,4,5-trisphosphate (InsP3) pathway. Ca2+ released through InsP3-dependent channels of the SR activates ryanodine receptors to amplify the cytosolic Ca2+ signal, thus triggering arterial cerebral vasoconstriction in the absence of extracellular calcium influx. This metabotropic action of L-type Ca2+ channels, denoted as calcium channel-induced Ca2+ release, could have implications in cerebral vascular pharmacology and pathophysiology, because it can be suppressed by Ca2+ channel antagonists and potentiated with small concentrations of extracellular vasoactive agents as ATP.