Regulation of calcium slow channels in cardiac muscle and vascular smooth muscle cells.

Abstract

Considerable attention during the past few years has been given to phosphorylation of ion channels as a means whereby the activity of the ion channels can be regulated. This article will cover the evidence that cyclic nucleotides regulate the Ca2+ influx into the myocardial cells during each cardiac cycle and into vascular smooth muscle (VSM) cells. This regulation is presumable mediated by phosphorylation(s) of the Ca2+ slow channel protein and/or of associated regulatory protein(s). In myocardial cells, such phosphorylation (Fig. 1) presumably (a) increases the number of Ca2+ slow channels available for voltage activation during the action potential (AP); (b) increases the probability of their opening, and (c) increases their mean open time. A greater density of available Ca2+ channels increases Ca2+ influx and inward Ca2+ slow current (Isi) during the AP, and so increases the force of contraction of the heart. In some VSM cells, phosphorylation by cAMP-PK or cGMP-PK inhibits the Ca2+ slow channel activity and thereby produces vasodilation, whereas phosphorylation by PK-C stimulates the Ca2+ slow channel activity and produces vasoconstriction.