Calcium signaling dysfunction in heart disease

In the heart, Ca2+ is crucial for the regulation of contraction and intracellular signaling, processes, which are vital to the functioning of the healthy heart. Ca2+-activated signaling pathways must function against a background of large, rapid, and tightly regulated changes in intracellular free Ca2+ concentrations during each contraction and relaxation cycle. This review highlights a number of proteins that regulate signaling Ca2+ in both normal and pathological conditions including cardiac hypertrophy and heart failure, and discusses how these pathways are not regulated by the marked elevation in free intracellular calcium ([Ca2+]i) during contraction but require smaller sustained increases in Ca2+ concentration. In addition, we present published evidence that the pool of Ca2+ that regulates signaling is compartmentalized into distinct cellular microdomains and is thus distinct from that regulating contraction. © 2011 International Union of Biochemistry and Molecular Biology, Inc.