Short Communication: Genetic Ablation of L-Type Ca2+ Channels Abolishes Depolarization-Induced Ca2+ Release in Arterial Smooth Muscle

M. Fernandez-Tenorio, P. Gonzalez-Rodriguez, C. Porras, A. Castellano, S. Moosmang, F. Hofmann, J. Urena, J. Lopez-Barneo
2010 Circulation Research  
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
more » ... larization 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. (Circ Res. 2010;106: 1285-1289.)
doi:10.1161/circresaha.109.213967 pmid:20299662 fatcat:ncqrpsyvivgjbho7wqzoylsjvm