Involvement of Ca2+ channel activity in proliferation of vascular smooth muscle cells

Proliferation of vascular smooth muscle (VSM) cells is a crucial step for developing vascular diseases such as atherosclerosis, hypertension and vascular restenosis after angioplasty. Proliferation of VSM cells is regulated by many intracellular signals: second messengers (e.g. Ca2+, phosphatydylinositol, cAMP/cGMP), protein kinases and transcription factors. Although Ca2+ regulation of cell proliferation is very important, there is rarely any informative review paper about the topic. Increase in cytosolic intracellular Ca2+ concentration ([Ca2+]i) due to Ca2+ entry is necessary for proliferation of VSM cells. Elevation of [Ca2+]i is needed for both cell cycle progressions at G1/S phase and the cell division in M phase. Intracellular Ca2+ is regulated by the balance between Ca2+-elevating machinery such as Ca2+ influx through voltage-dependent Ca2+ channels (VDCC), Ca2+ release from stored Ca2+ in sarcoplasmic reticulum and Ca2+-lowering machinery such as Ca2+ transport ATPases. In this review paper, we focus on the role of VDCC in the regulation of cell proliferation, especially in VSM cells. We also described significant roles of VDCC in pathophysiological conditions such as atherosclerosis, stroke and renal dysfunction.