Regulation of Calcium Slow Channels in Myocardial Cells by Cyclic Nucleotides and Phosphorylation

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 that occurs during each cardiac cycle. This regulation is presumably mediated by phosphorylation(s) of the Ca2+ slow channel protein (L-type) and/or of associated regulatory protein(s). In myocardial cells, phosphorylation of the slow Ca channels (or of an associated regulatory protein) by cAMP-PK (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 (Ica) during the AP, and so increases the force of contraction of the heart. Phosphorylation by cGMP-PK depresses the activity of the slow Ca channels [1,2, 3].