Metabotropic regulation of RhoA/Rho-associated kinase by L-type Ca2+ channels.
Sustained vascular smooth muscle contraction can be mediated by several mechanisms, including the influx of extracellular Ca(2+) through L-type voltage-gated Ca(2+) channels (LTCCs) and by RhoA/Rho-associated kinase (ROCK)-dependent Ca(2+) sensitization of the contractile machinery. Conformational changes in the LTCC following depolarization can also trigger an ion-independent metabotropic pathway that involves G protein/phospholipase C activation, giving rise to inositol 1,4,5-trisphosphate synthesis and subsequent Ca(2+) release from the sarcoplasmic reticulum (SR) (calcium channel-induced Ca(2+) release or calcium channel-induced calcium release [CCICR]). In this review, we summarize recent data suggesting that LTCC activation and subsequent metabotropic Ca(2+) release from the SR participate in depolarization-evoked RhoA/ROCK activity and sustained arterial contraction. During protracted depolarizations, refilling of the SR stores by a residual influx of extracellular Ca(2+) through LTCCs helps maintain RhoA activity and contractile activation. These findings suggest that CCICR plays a major role in tonic vascular smooth muscle contraction, providing a link between membrane depolarization-induced LTCC activation and metabotropic Ca(2+) release and RhoA/ROCK stimulation.
Instituto de Biomedicina de Sevilla (IBiS) and Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen de Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. jurena@us.es
Juan
J
Ureña
José
J
López-Barneo
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D020746:Calcium Channels, L-Type; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D002118:Calcium