Short communication: genetic ablation of L-type Ca2+ channels abolishes depolarization-induced Ca2+ release in arterial smooth muscle.

Abstract

In arterial myocytes, membrane depolarization-induced Ca(2+) release (DICR) from the sarcoplasmic reticulum (SR) occurs through a metabotropic pathway that leads to inositol trisphosphate synthesis independently of extracellular Ca(2+) influx. Despite the fundamental functional relevance of DICR, its molecular bases are not well known. Biophysical and pharmacological data have suggested that L-type Ca(2+) channels could be the sensors coupling membrane depolarization to SR Ca(2+) release. This hypothesis was tested using smooth muscle-selective conditional Ca(v)1.2 knockout mice. In aortic myocytes, the decrease of Ca(2+) channel density was paralleled by the disappearance of SR Ca(2+) release induced by either depolarization or Ca(2+) channel agonists. Ca(v)1.2 channel deficiency resulted in almost abolition of arterial ring contraction evoked by DICR. Ca(2+) channel-null cells showed unaltered caffeine-induced Ca(2+) release and contraction. These data suggest that Ca(v)1.2 channels are indeed voltage sensors coupled to the metabolic cascade, leading to SR Ca(2+) release. These findings support a novel, ion-independent, functional role of L-type Ca(2+) channels linked to intracellular signaling pathways in vascular myocytes.