Calmodulin and CaMKII as molecular switches for cardiac ion channels

Because changes in intracellular Ca2+ concentration are the final signals of electrical activity in excitable cells, many mechanisms have evolved to regulate Ca2+ influx. Among the most important are those pathways that directly regulate the ion channels responsible for regulating and generating the Ca2+ influx signal. Recent work has demonstrated that the Ca2+ binding protein calmodulin (CaM) and the Ca2+/CaM-sensitive kinase CaMKII are important modulators of cardiac ion channels. Thus, Ca2+ participates in feedback modulation to control electrical activity. This review highlights various mechanisms by which CaM and CaMKII regulate cardiovascular ion channel activity and presents a novel model for CaMKII regulation of Ca(V)1.2 Ca2+ channel function. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.