This review outlines the fundamental mechanisms of calcium homeostasis and activation in vascular smooth muscle contraction.
The primary stimulus for activation of vascular smooth muscle is an increase in the cytosolic free Ca2+ concentration. The level of activating Ca2+ is determined by a variety of Ca2+ homeostatic mechanisms. Ca2+ entry from the extracellular space occurs through the resting Ca2+ leak and the excitable Ca2+ channels: viz. voltage-gated, receptor-operated and stretch-activated channels. Ca2+ release from sarcoplasmic reticulum is induced by inositol triphosphate (IP3) and, possibly, by Ca2+ itself. Activating Ca2+ binds to calmodulin, forming a complex which induces myosin light chain phosphorylation and initiates smooth muscle contraction. The continuous Ca2+ entry together with the higher Ca2+ sensitivity of the contractile apparatus can then maintain smooth muscle tension. Ca2+ buffering by the sarcoplasmic reticulum and Ca2+ extrusion by Ca2+ pumps serve to lower the cytosolic free Ca2+ concentration. These Ca2+-lowering mechanisms are possibly regulated by cyclic nucleotides.
Khalil et al. (Tue,) studied this question.