Calmodulin and CaMKII as molecular switches for cardiac ion channels.
Because changes in intracellular Ca(2+) concentration are the final signals of electrical activity in excitable cells, many mechanisms have evolved to regulate Ca(2+) influx. Among the most important are those pathways that directly regulate the ion channels responsible for regulating and generating the Ca(2+) influx signal. Recent work has demonstrated that the Ca(2+) binding protein calmodulin (CaM) and the Ca(2+)/CaM-sensitive kinase CaMKII are important modulators of cardiac ion channels. Thus, Ca(2+) 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 Ca(2+) channel function.
Pitt
Geoffrey S
GS
Department of Medicine, Division of Cardiology, College of Physicians and Surgeons of Columbia University, 630 W 168th St, PH 7W 318, New York, NY 10032, USA. gp2004@columbia.edu
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D008958:Models, Molecular; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D020746:Calcium Channels, L-Type; D002147:Calmodulin; D007473:Ion Channels; D024681:Potassium Channels, Calcium-Activated; D019837:Ryanodine Receptor Calcium Release Channel; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases