Calmodulin and CaMKII as Ca2+ Switches for Cardiac Ion Channels

Changes in intracellular Ca²⁺ are among the most diverse and important means of cell signaling. In the heart, signaling pathways from excitation-contraction coupling to humoral activation of hypertrophic responses all rely on changes in the concentration of intracellular Ca²⁺. Ion channels belong to a class of signaling proteins that is particularly sensitive to a change in intracellular Ca²⁺, which is the final signal of all coordinated ion channel activity. Thus, regulation of ion channel function by Ca²⁺ provides an essential feedback mechanism for cellular electrical activity. Two intracellular proteins activated by Ca²⁺, the ubiquitous Ca²⁺ binding protein calmodulin (CaM), and the Ca²⁺/CaM-dependent protein kinase CaMKII, dictate most of the actions of intracellular Ca²⁺ on cardiac ion channels. In this chapter, we highlight key roles for CaM and CaMKII in cardiac myocytes as downstream integrators of Ca²⁺ signals in the regulation of cardiac ion channels and consequent actions on myocyte excitability. © 2014 Elsevier Inc. All rights reserved.

Duke Scholars

Author Geoffrey Stuart Pitt Medicine, Cardiology