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 A2in ECs to regulate nitric oxide (NO) and prostaglandin I2formation. Understanding of the importance of SR or ER in modulating the [Ca2+]iin 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 Ca2+-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. It appears that SR has multiple roles in maintaining the homeostasis of cytosolic Ca2+, which controls the VSM tone directly or indirectly via ECs. These roles include (i) activation of phasic contraction of VSM by opening of the Ca2+release channels, (ii) acting as a sink for entering Ca2+when the Ca2+stores are depleted, extruding Ca2+when the Ca2+stores are refilled, and (iii) signalling and regulating the amount of Ca2+entry in relation to the degree of filling of the store. This symposium concensus paper reflects current thoughts on the above roles of SR–ER in the control of cytosolic Ca2+concentration, and thus the regulation of vascular tone.Key words: calcium channels, calcium pumps, sarcoplasmic reticulum, plasma membranes, vascular smooth muscle, endothelial cell.