Mechanisms of Altered Ca2+ Handling in Heart Failure

Ca plays a crucial role in connecting membrane excitability with contraction in myocardium. The hallmark features of heart failure are mechanical dysfunction and arrhythmias; defective intracellular Ca homeostasis is a central cause of contractile dysfunction and arrhythmias in failing myocardium. Defective Ca homeostasis in heart failure can result from pathological alteration in the expression and activity of an increasingly understood collection of Ca homeostatic and structural proteins, ion channels, and enzymes. This review focuses on the molecular mechanisms of defective Ca cycling in heart failure and considers how fundamental understanding of these pathways may translate into novel and innovative therapies.