Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8260851 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2013 | 7 Pages |
Abstract
Sarcoplasmic reticulum (SR) Ca2Â + release plays an essential role in mediating cardiac myocyte contraction. Depolarization of the plasma membrane results in influx of Ca2Â + through l-type Ca2Â + channels (LTCCs) that in turn triggers efflux of Ca2Â + from the SR through ryanodine receptor type-2 channels (RyR2). This process known as Ca2Â +-induced Ca2Â +release (CICR) occurs within the dyadic region, where the adjacent transverse (T)-tubules and SR membranes allow RyR2 clusters to release SR Ca2Â + following Ca2Â + influx through adjacent LTCCs. SR Ca2Â + released during systole binds to troponin-C and initiates actin-myosin cross-bridging, leading to muscle contraction. During diastole, the cytosolic Ca2Â + concentration is restored by the resequestration of Ca2Â + into the SR by SR/ER Ca2Â +-ATPase (SERCA2a) and by the extrusion of Ca2Â + via the Na+/Ca2Â +-exchanger (NCX1). This whole process, entitled excitation-contraction (EC) coupling, is highly coordinated and determines the force of contraction, providing a link between the electrical and mechanical activities of cardiac muscle. In response to heart failure (HF), the heart undergoes maladaptive changes that result in depressed intracellular Ca2Â + cycling and decreased SR Ca2Â + concentrations. As a result, the amplitude of CICR is reduced resulting in less force production during EC coupling. In this review, we discuss the specific proteins that alter the regulation of Ca2Â + during HF. In particular, we will focus on defects in RyR2-mediated SR Ca2Â + release. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.
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Authors
Sameer Ather, Jonathan L. Respress, Na Li, Xander H.T. Wehrens,