Mechanisms of altered Ca²⁺ handling in heart failure.

Ca²⁺ 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 Ca²⁺ homeostasis is a central cause of contractile dysfunction and arrhythmias in failing myocardium. Defective Ca²⁺ homeostasis in heart failure can result from pathological alteration in the expression and activity of an increasingly understood collection of Ca²⁺ homeostatic and structural proteins, ion channels, and enzymes. This review focuses on the molecular mechanisms of defective Ca²⁺ cycling in heart failure and considers how fundamental understanding of these pathways may translate into novel and innovative therapies.