Leung F P, Yung L M, Yao X, Laher I, Huang Y
Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Br J Pharmacol. 2008 Mar;153(5):846-57. doi: 10.1038/sj.bjp.0707455. Epub 2007 Sep 17.
In non-excitable cells, activation of G-protein-coupled phospholipase C (PLC)-linked receptors causes the release of Ca(2+) from intracellular stores, which is followed by transmembrane Ca(2+) entry. This Ca(2+) entry underlies a small and sustained phase of the cellular Ca(2+) increases and is important for several cellular functions including gene expression, secretion and cell proliferation. This form of transmembrane Ca(2+) entry is supported by agonist-activated Ca(2+)-permeable ion channels that are activated by store depletion and is referred to as store-operated Ca(2+) entry (SOCE) and represents a major pathway for agonist-induced Ca(2+) entry. In excitable cells such as smooth muscle cells, Ca(2+) entry mechanisms responsible for sustained cellular activation are normally considered to be mediated via either voltage-operated or receptor-operated Ca(2+) channels. Although SOCE occurs following agonist activation of smooth muscle, this was thought to be more important in replenishing Ca(2+) stores rather than acting as a source of activator Ca(2+) for the contractile process. This review summarizes our current knowledge of SOCE as a regulator of vascular smooth muscle tone and discusses its possible role in the cardiovascular function and disease. We propose a possible hypothesis for its activation and suggest that SOCE may represent a novel target for pharmacological therapeutic intervention.
在非兴奋性细胞中，G蛋白偶联磷脂酶C（PLC）相关受体的激活会导致细胞内储存的Ca(2+)释放，随后是跨膜Ca(2+)内流。这种Ca(2+)内流是细胞内[Ca(2+)]i小幅持续增加阶段的基础，对包括基因表达、分泌和细胞增殖在内的多种细胞功能很重要。这种跨膜Ca(2+)内流形式由激动剂激活的Ca(2+)可渗透离子通道支持，这些通道由储存耗竭激活，被称为储存操纵性Ca(2+)内流（SOCE），是激动剂诱导Ca(2+)内流的主要途径。在平滑肌细胞等兴奋性细胞中，负责细胞持续激活的Ca(2+)内流机制通常被认为是通过电压门控或受体门控Ca(2+)通道介导的。虽然SOCE在平滑肌激动剂激活后发生，但人们认为它在补充Ca(2+)储存方面比作为收缩过程中激活剂Ca(2+)的来源更重要。这篇综述总结了我们目前对SOCE作为血管平滑肌张力调节剂的认识，并讨论了其在心血管功能和疾病中的可能作用。我们提出了其激活的一个可能假设，并表明SOCE可能代表了药物治疗干预的一个新靶点。
