Calcium signaling dysfunction in heart disease

Abstract

In the heart, Ca(2+) is crucial for the regulation of contraction and intracellular signaling, processes, which are vital to the functioning of the healthy heart. Ca(2+) -activated signaling pathways must function against a background of large, rapid, and tightly regulated changes in intracellular free Ca(2+) concentrations during each contraction and relaxation cycle. This review highlights a number of proteins that regulate signaling Ca(2+) 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 ([Ca(2+) ](i)) during contraction but require smaller sustained increases in Ca(2+) concentration. In addition, we present published evidence that the pool of Ca(2+) that regulates signaling is compartmentalized into distinct cellular microdomains and is thus distinct from that regulating contraction.

Cantú Syndrome Is Caused by Mutations in ABCC9

“…19 Correct maintenance of calcium handling is essential for the normal functioning of the heart, and dysfunctional myocellular calcium homeostasis contributes to the pathogenesis of dilated cardiomyopathy (CMD10 [MIM 608569]). [22][23][24] In Sur2 À/À mice, K ATP channel activity is essentially absent, and these animals show hypertension, coronary artery vasospasm, and sudden cardiac death.…”

Ca2+-dependent Transcriptional Control of Ca2+ Homeostasis

“…In some cases, these self-regulatory processes involve parallel compensatory changes in several Ca 2ϩ regulatory proteins so that increases or decreases in intracellular stores and cytosolic Ca 2ϩ levels slowly adjust the concentrations of key signaling pathway components (3). In other cases, components of the homeostasis machinery are coordinately modified to respond to chronic pathological conditions as in end stages of heart failure (4,5) or in neurodegenerative processes. Thus, in Huntington disease striatal neurons accumulate changes in the expression of most, if not all, genes related to Ca 2ϩ homeostasis (6).…”

Myocardial calcium signaling in physiology and disease

“…Emerging studies reveal that these Ca 2+ -dependent responses are temporally mediated by distinct Ca 2+ pools (ie, microdomains), which are generated by diverse channels with widely differing timescales of activation. [4][5][6] In this review, we discuss how myocardial Ca 2+ signaling is essential for proper and coordinated cardiomyocyte function, as aberrant Ca…”