FERNANDEZ TENORIO, MIGUEL, Gonzalez-Rodriguez, Patricia , Porras, Cristina , Castellano, Antonio , Moosmang, Sven , Hofmann, Franz , Urena, Juan , Lopez-Barneo, Jose
No
Circ.Res.
Article
Científica
9.504
5.615
16/04/2010
000276728700014
Rationale: In arterial myocytes, membrane depolarization-induced Ca2+ release (DICR) from the sarcoplasmic reticulum (SR) occurs through a metabotropic pathway that leads to inositol trisphosphate synthesis independently of extracellular Ca2+ 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 Ca2+ channels could be the sensors coupling membrane depolarization to SR Ca2+ 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 Ca2+ channel density was paralleled by the disappearance of SR Ca2+ release induced by either depolarization or Ca2+ channel agonists. Ca(v)1.2 channel deficiency resulted in almost abolition of arterial ring contraction evoked by DICR. Ca2+ channel-null cells showed unaltered caffeine-induced Ca2+ 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 Ca2+ release. These findings support a novel, ion-independent, functional role of L-type Ca2+ channels linked to intracellular signaling pathways in vascular myocytes. (Circ Res. 2010;106:1285-1289.)
membrane depolarization; Ca2+ release; Ca(v)1.2 channel knockout; arterial smooth muscle; voltage sensors