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.