title: A new metabotropic role for L-type Ca(2+) channels in vascular smooth muscle contraction.
abstract: Vascular smooth muscle cells (VSMCs) contraction can be evoked by the rise of cytosolic [Ca(2+)] owing to transmembrane Ca(2+) influx or sarcoplasmic reticulum (SR) Ca(2+) release. Although the classical ionotropic role of voltagedependent (L-type) Ca(2+) channels (VGCCs) is known, we review here data suggesting a new metabotropic function of VGCCs in vascular smooth muscle cells. VGCCs can trigger Ca(2+) 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 (InsP3) pathway leading to Ca2+ release and arterial contraction. This new metabotropic role of VGCCs, referred as calcium channel-induced Ca(2+) release (CCICR), has a major role in tonic VSM contractility, as it links sustained membrane depolarization and Ca(2+) channel activation with metabotropic Ca(2+) 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 Ca(2+) channels antagonists are recommended.
authors.affiliation: Instituto de Biomedicina de Sevilla and Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. jurena@us.es
authors.forename: Juan
authors.initials: J
authors.lastname: Ureña
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Tenorio
authors.forename: Cristina
authors.initials: C
authors.lastname: Porras-González
authors.forename: Patricia
authors.initials: P
authors.lastname: González-Rodríguez
authors.forename: Antonio
authors.initials: A
authors.lastname: Castellano
authors.forename: José
authors.initials: J
authors.lastname: López-Barneo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium