Rationale : 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. Objective : 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. Methods and Results : 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. Conclusion : 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.