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(Circulation. 2005;111:906-912.)
© 2005 American Heart Association, Inc.

Molecular Cardiology

Myosin-Binding Protein C Phosphorylation, Myofibril Structure, and Contractile Function During Low-Flow Ischemia

Robert S. Decker, PhD; Marlene L. Decker, AA; Irina Kulikovskaya, PhD; Sakie Nakamura, MS; Daniel C. Lee, MD; Kathleen Harris, BA; Francis J. Klocke, MD; Saul Winegrad, MD

From the Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Ill (R.S.D., M.L.D., S.N., D.C.L., K.H., F.J.K.), and Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia (I.K., S.W.).

Correspondence to Dr Robert S. Decker, Feinberg Cardiovascular Research Institute, Tarry 12-733, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL 60611-3008. E-mail r-decker{at}northwestern.edu

Received June 29, 2004; revision received September 22, 2004; accepted October 6, 2004.

Background— Contractile dysfunction develops in the chronically instrumented canine myocardium after bouts of low-flow ischemia and persists after reperfusion. The objective of this study is to identify whether changes in the phosphorylation state of myosin-binding protein C (MyBP-C) are a potential cause of dysfunction.

Methods and Results— During low-flow ischemia, MyBP-C is dephosphorylated, and the number of actomyosin cross-bridges in the central core of the sarcomere decreases as thick filaments dissemble from the periphery of the myofibril. During reperfusion, MyBP-C remains dephosphorylated, and its degradation is accelerated.

Conclusions— Dephosphorylation of MyBP-C may initiate changes in myofibril thick filament structure that decrease the interaction of myosin heads with actin thin filaments. Limiting the formation of actomyosin cross-bridges may contribute to the contractile dysfunction that is apparent after low-flow ischemia. Breakdown of MyBP-C during reperfusion may prolong myocardial stunning.

Key Words: myocytes • myosins • phosphorylation • contractility • ischemia

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