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(Circulation Research. 2008;102:1301.)
© 2008 American Heart Association, Inc.

Editorials

The Ins and Outs of Calcium in Heart Failure

Brian O'Rourke

From The Johns Hopkins University, School of Medicine, Division of Cardiology, Baltimore, Md.

Correspondence to Brian O'Rourke, PhD, The Johns Hopkins University, Institute of Molecular Cardiobiology, 720 Rutland Ave, 1059 Ross Bldg, Baltimore, MD 21205-2195. E-mail bor@jhmi.edu

See related article, pages 1398–1405

Key Words: excitation–contraction coupling • sodium–calcium exchange • SERCA2A • SEA-0400 • KB-R7943 • NCX inhibitors

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Cardiac excitation–contraction coupling is akin to a biophysical juggling act that involves fast and slow ion movements overlapping in time and space across several compartments. In response to sarcolemmal depolarization, Ca²⁺ release from the large intracellular store in the sarcoplasmic reticulum (SR) is triggered by a rush of Ca²⁺ from the extracellular space through L-type Ca²⁺ channels into the very tiny junctional cleft (12 nm) to activate SR Ca²⁺ release channels in a tightly controlled signal amplification step. Local inactivation of the L-type Ca²⁺ channel mediated by the large junctional Ca²⁺ spike (peaking at >50 µmol/L) provides a mechanism of negative feedback on beat-to-beat Ca²⁺ influx; thus, an abrupt change in the size of cytosolic Ca²⁺ transient will impact the trigger for subsequent beats and reciprocally influence the SR Ca²⁺ content in a process known as autoregulation.¹

Ca²⁺ removal processes, although kinetically slower, also play a major role in shaping the Ca²⁺ dynamics, and, ultimately, the contraction, of the myocyte. The 2 main pathways, Ca²⁺ reuptake into the SR by the Ca²⁺ ATPase (SERCA2A) and Ca²⁺ efflux across the sarcolemma by the Na⁺/Ca²⁺ exchanger (NCX), compete for the job of removing Ca²⁺ ions in a species-dependent manner. In ventricular myocytes from rats and mice, 90% of the Ca²⁺ decline during a transient is mediated by SERCA2A, whereas NCX contributes only 7% to Ca²⁺ removal (the remainder is taken up by mitochondria or extruded from the cell by the sarcolemmal Ca²⁺ ATPase).² In most large animals (eg, rabbits, dogs, cats, . . . [Full Text of this Article]

Related Article:

Pharmacological Inhibition of Na/Ca Exchange Results in Increased Cellular Ca²⁺ Load Attributable to the Predominance of Forward Mode Block

Semir Ozdemir, Virginie Bito, Patricia Holemans, Laurent Vinet, Jean-Jacques Mercadier, Andras Varro, and Karin R. Sipido
Circ. Res. 2008 102: 1398-1405. [Abstract] [Full Text] [PDF]

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