Store‐operated calcium entry in vascular smooth muscle

In non‐excitable cells, activation of G‐protein‐coupled phospholipase C (PLC)‐linked receptors causes the release of Ca2+ from intracellular stores, which is followed by transmembrane Ca2+ entry. This Ca2+ entry underlies a small and sustained phase of the cellular [Ca2+]i increases and is important for several cellular functions including gene expression, secretion and cell proliferation. This form of transmembrane Ca2+ entry is supported by agonist‐activated Ca2+‐permeable ion channels that are activated by store depletion and is referred to as store‐operated Ca2+ entry (SOCE) and represents a major pathway for agonist‐induced Ca2+ entry. In excitable cells such as smooth muscle cells, Ca2+ entry mechanisms responsible for sustained cellular activation are normally considered to be mediated via either voltage‐operated or receptor‐operated Ca2+ channels. Although SOCE occurs following agonist activation of smooth muscle, this was thought to be more important in replenishing Ca2+ stores rather than acting as a source of activator Ca2+ 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. British Journal of Pharmacology (2008) 153, 846–857; doi:10.1038/sj.bjp.0707455; published online 17 September 2007