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(Circulation Research. 2005;97:1213.)
© 2005 American Heart Association, Inc.

Editorials

The Fire From Within

The Biggest Ca²⁺ Channel Erupts and Dribbles

Mark E. Anderson

From the University of Iowa, Carver College of Medicine, Iowa City.

Correspondence to Mark E. Anderson, MD, PhD, University of Iowa, Carver College of Medicine, 200 Hawkins Drive, Room E 315 GH, Iowa City, IA 53342-1081. E-mail mark-e-anderson@uiowa.edu

See related article, pages 1314–1322

Key Words: calmodulin kinase II • ryanodine receptor • heart failure • arrhythmias

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

	CaMKII Is a Pluripotent Signaling Molecule in Heart

 
The multifunctional Ca²⁺ and calmodulin (CaM)-dependent protein kinase II (CaMKII) is a serine threonine kinase that is abundant in heart where it phosphorylates Ca²⁺_i homeostatic proteins. It seems likely that CaMKII plays an important role in cardiac physiology because these target proteins significantly overlap with the more extensively studied serine threonine kinase, protein kinase A (PKA), which is a key arbiter of catecholamine responses in heart. However, the physiological functions of CaMKII remain poorly understood, whereas the potential role of CaMKII in signaling myocardial dysfunction and arrhythmias has become an area of intense focus. CaMKII activity and expression are upregulated in failing human hearts and in many animal models of structural heart disease.¹ CaMKII inhibitory drugs can prevent cardiac arrhythmias^2,3 and suppress afterdepolarizations⁴ that are a probable proximate focal cause of arrhythmias in heart failure. CaMKII inhibition in mice reduces left ventricular dilation and prevents disordered intracellular Ca²⁺ (Ca²⁺_i) homeostasis after myocardial infarction.⁵ CaMKII overexpression in mouse heart causes severe cardiac hypertrophy, dysfunction, and sudden death that is heralded by increased SR Ca²⁺ leak⁶; these findings go a long way to making a case for CaMKII as a causative signal in heart disease and arrhythmias but do not identify critical molecular targets or test the potential role of CaMKII in a large non-rodent animal model. The work by Ai et al in this issue of Circulation Research makes an important contribution by demonstrating CaMKII upregulation causes increased Ca²⁺ leak from ryanodine receptor (RyR) Ca²⁺ release channels in a . . . [Full Text of this Article]

Related Article:

Ca²⁺/Calmodulin–Dependent Protein Kinase Modulates Cardiac Ryanodine Receptor Phosphorylation and Sarcoplasmic Reticulum Ca²⁺ Leak in Heart Failure

Xun Ai, Jerry W. Curran, Thomas R. Shannon, Donald M. Bers, and Steven M. Pogwizd
Circ. Res. 2005 97: 1314-1322. [Abstract] [Full Text] [PDF]