Involvement of Ca(2+) 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. Ca(2+), phosphatydylinositol, cAMP/cGMP), protein kinases and transcription factors. Although Ca(2+) regulation of cell proliferation is very important, there is rarely any informative review paper about the topic. Increase in cytosolic intracellular Ca(2+) concentration ([Ca(2+)](i)) due to Ca(2+) entry is necessary for proliferation of VSM cells. Elevation of [Ca(2+)](i) is needed for both cell cycle progressions at G(1)/S phase and the cell division in M phase. Intracellular Ca(2+) is regulated by the balance between Ca(2+)-elevating machinery such as Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCC), Ca(2+) release from stored Ca(2+) in sarcoplasmic reticulum and Ca(2+)-lowering machinery such as Ca(2+) 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.