Vascular Smooth Muscle Cells (VSMCs) form a major structural and functional layer in the blood vessel wall. The contractile state of these cells determines vascular tone and consequently tissue perfusion. Vascular contraction is initiated by the Ca2+/Calmodulin-dependent activation of myosin light chain kinase resulting in the interaction of actin and myosin and consequent cross bridge cycling. Cytosolic free Ca2+ ([Ca2+]cyt) is therefore the key second messenger activating vascular contraction and its regulation is vital in the control of vascular tone.
Elevations of [Ca2+]cyt in VSMCs are chiefly mediated by voltage-gated L- and T-type Ca2+ channels and receptor-operated Ca2+ permeable channels. Receptor-operated channels include second messenger-activated non-selective cation channels on the plasma membrane and membranes of intracellular organelles and store-operated Ca2+ channels. Recent evidence suggests that VSMCs express stromal interacting molecule 1 (STIM1) and Orai1 proteins, which form a certain type of store-operated channels on the plasma membrane, called Ca2+ release activated Ca2+ (CRAC) channels (Potier, et al., 2009; Hoth & Penner, 1992). Although initially characterised exclusively in non-excitable cells, CRAC channels have been recently shown to be present in skeletal and smooth muscle cells and other excitable tissues, where they interact with L-type voltage-gated Ca2+ channels and Transient Receptor Potential channels and contribute to specific cellular functions and regulation of intracellular Ca2+ signals (Wang, et al., 2010; Dirksen, 2009).It has been suggested that CRAC channels are required for VSMCs proliferation and migration following vascular injury, and may contribute to the development of hypertension (Potier, et al., 2009; Giachini, et al., 2010). However, the exact contribution of CRAC channels to the regulation of vascular tone and receptor-mediated VSMCs contractions is not well understood.
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