Regulation of vascular tone: cross-talk between sarcoplasmic reticulum and plasmalemma

Abstract

Selected topics on the roles of sarcoplasmic reticulum (SR) in the control of vascular smooth muscle (VSM) tone are briefly reviewed with particular reference to the regulation of cytosolic concentration of free calcium ions, [Ca2+]i. Although morphological evidence and subcellular membrane studies indicate a relatively meager quantity of SR in VSM and of endoplasmic reticulum (ER) in endothelial cells (ECs) compared with skeletal muscle and cardiac muscle, contractility studies suggest that vascular tone is, to a large extent, regulated by the intracellular Ca2+ stores in smooth muscle and endothelial cells. Cytosolic Ca2+ levels control myosin light chain phosphorylation and contraction in VSM and activation of NO synthase and phospholipase A2 in ECs to regulate nitric oxide (NO) and prostaglandin I2 formation. Understanding of the importance of SR or ER in modulating the [Ca2+]i in VSM and ECs has been further advanced as a result of the new development and refinement of biophysical techniques in the measurement of cellular Ca2+ concentrations and ion currents, such as fluorescent Ca2+ indicators and patch-clamp techniques. Experimental evidence has accumulated in support of the existence of cross-talk between SR-ER and the plasma membrane (PM). Novel pharmacological tool drugs selective for the SR-ER Ca2+ pump, such as thapsigargin and cyclopiazonic acid, as well as for SR-ER Ca2+ channels, such as ryanodine (for the Ca(2+)-induced Ca2+ release channel) and inositol polyphosphates and heparin (for the inositol-1,4,5-trisphosphate activated Ca2+ channel), together with the use of blockers for selective PM Ca2+ channels have enabled better formulation and elucidation of the mechanisms of cross-talk between SR-ER and PM.(ABSTRACT TRUNCATED AT 250 WORDS)