Urena, Juan , FERNANDEZ TENORIO, MIGUEL, Porras-Gonzalez, Cristina , Gonzalez-Rodriguez, Patricia , Castellano, Antonio , Lopez-Barneo, Jose
No
Current Vascular Pharmacology
Article
Científica
2.908
0.783
01/07/2013
000322265300012
Vascular smooth muscle cells (VSMCs) contraction can be evoked by the rise of cytosolic [Ca2+] owing to transmembrane Ca2+ influx or sarcoplasmic reticulum (SR) Ca2+ release. Although the classical ionotropic role of voltage-dependent (L-type) Ca2+ channels (VGCCs) is known, we review here data suggesting a new metabotropic function of VGCCs in vascular smooth muscle cells. VGCCs can trigger Ca2+ release from the SR in the absence of extracellular Ca2+. During depolarization, VGCCs can activate G proteins and phospholipase C (PLC)/inositol 1,4,5-trisphosphate (InsP(3)) pathway leading to Ca2+ release and arterial contraction. This new metabotropic role of VGCCs, referred as calcium channel-induced Ca2+ release (CCICR), has a major role in tonic VSM contractility, as it links sustained membrane depolarization and Ca2+ channel activation with metabotropic Ca2+ release from the sarcoplasmic reticulum (SR) and tonic smooth muscle contraction. This new role of VGCCs could have a wide functional relevance for the pathogenesis of vasospasms mediated by membrane depolarization and vasoactive agents that can activate VGCCs. Precise understanding of CCICR could help to optimize pharmacological treatments for clinical conditions where Ca2+ channels antagonists are recommended.
Vascular smooth muscle; L-type Ca2+ channels; sarcoplasmic reticulum; depolarization-induced Ca2+ release; arterial contraction