Ca2+, calmodulin, and cyclins in vascular smooth muscle cell cycle.

Ca 2 is a major determinant of many biochemical processes in various cell types, from the beginning of new life and egg fertilization to the end of life and cell death.1 In vascular smooth muscle (VSM), physiological resting levels of intracellular free Ca concentration ([Ca ]i) in the nanomolar range are necessary to maintain basal vascular tone.2–4 VSM activation is associated with an increase in [Ca ]i in the micromolar range,2–4 and large increases in VSM [Ca ]i have been identified in excessive vasoconstriction disorders such as hypertension and coronary vasospasm.2,5 Activation of surface membrane receptors in VSM triggers increases in [Ca ]i attributable to Ca release from the intracellular stores in the sarcoplasmic reticulum and Ca entry from the extracellular space through Ca channels (see Figure). Ca then activates specific protein kinases and phosphatases that are involved in VSM contraction and relaxation.2,3,6 Ca may also function as a second messenger to activate other signaling pathways such as cytosolic phospholipase A2 , phospholipase C, protein kinase C and phosphodiesterase.6–8 An increase in [Ca ]i could also modulate plasma membrane channels and pumps such as Ca activated K channels and the plasma membrane CaATPase (PMCA).9,10 Additionally, Ca may affect sarcoplasmic reticulum channels and pumps such as the inositol 1,4,5trisphosphate (IP3) receptor, the ryanodine-sensitive receptor and intracellular Ca release channels, and the Ca uptake pump (SERCA).11,12