Calcium activation of vascular smooth muscle. State of the art lecture.

Abstract

Tension development in arterial smooth muscle is regulated by variations of calcium concentration in the submicromolar range. The receptor for Ca2+ is calmodulin, which through stimulation of myosin light chain kinase can activate sequentially two apparently different contractile states. A third possible contractile state may be related to C-kinase activation. These contractile states are thought to have different Ca2+ sensitivities. Ca2+ is supplied from two major sources: the sarcoplasmic reticulum and the extracellular space. The release of sarcoplasmic reticulum Ca2+ is mediated by the intracellular messenger inositol-1,4,5-trisphosphate (IP3) and perhaps by Ca2+ itself. These two messengers have the potential for amplification; for example, IP3 may release some Ca2+ that may subsequently cause Ca2+-induced Ca2+ release. The entry of Ca2+ from the extracellular space into the cytoplasm is mediated by a Ca2+ leak and by excitable Ca2+ channels and is modulated by a Ca2+ buffer barrier consisting of the superficial sarcoplasmic reticulum. Two types of adenosine 5'-triphosphate-driven Ca2+ pumps in the sarcoplasmic reticulum and plasmalemma are responsible for returning the cytoplasmic Ca2+ concentration to resting level after contraction and for maintaining Ca2+ homeostasis during the life of the cells.