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.
Trends Cardiovasc Med. 2012 Aug;22(6):155-60. doi: 10.1016/j.tcm.2012.07.013. Epub 2012 Aug 16.
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.
持续的血管平滑肌收缩可以通过多种机制介导，包括通过 L 型电压门控钙通道（LTCC）的细胞外 Ca(2+)内流，以及 RhoA/Rho 相关激酶（ROCK）依赖性收缩机制的 Ca(2+)敏感化。去极化后 LTCC 的构象变化也可以触发一种离子非依赖性代谢途径，该途径涉及 G 蛋白/磷脂酶 C 激活，导致肌醇 1,4,5-三磷酸（inositol 1,4,5-trisphosphate，IP3）的合成和随后的肌浆网（sarcoplasmic reticulum，SR）中的 Ca(2+)释放（钙通道诱导的 Ca(2+)释放或钙通道诱导的钙释放[CCICR]）。在这篇综述中，我们总结了最近的数据，这些数据表明 LTCC 的激活以及随后 SR 中的代谢性 Ca(2+)释放参与了去极化引发的 RhoA/ROCK 活性和持续的动脉收缩。在长时间的去极化过程中，通过 LTCC 残余的细胞外 Ca(2+)内流来补充 SR 储存，有助于维持 RhoA 活性和收缩激活。这些发现表明 CCICR 在血管平滑肌的紧张性收缩中起着重要作用，为膜去极化诱导的 LTCC 激活以及代谢性 Ca(2+)释放和 RhoA/ROCK 刺激之间提供了联系。
