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(Circulation Research. 2006;99:795.)
© 2006 American Heart Association, Inc.

Editorials

New Insights in the Role of Cardiac Myosin Binding Protein C As a Regulator of Cardiac Contractility

Henk L. Granzier, Kenneth B. Campbell

From the Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology (H.L.G., K.B.C.), Washington State University, Wash.

Correspondence to Henk L. Granzier, Department VCAPP, Washington State University, Pullman, WA 99164-6520. E-mail granzier@wsu.edu

See related article, pages 884–890

Key Words: stretch activation • ß–adrenergic stimulation • crossbridge kinetics • cooperativity

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

Myosin Binding Protein C is a large multidomain protein that is found in the A-band region of the sarcomere where it associates with the thick filament.¹ Mutations in cardiac myosin binding protein C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy² but the functions of cMyBP-C are not well resolved. In this issue Moss and colleagues (Stelzer et al³) provide important new insights in the role of cMyBP-C in the regulation of cardiac muscle contraction.

A binding site for the light meromyosin (LMM) domain of myosin is found near the C-terminus of MyBP-C and a second site that binds the S2 domain of myosin is present near the N-terminus of MyBP-C.⁴ The cardiac MyBP-C isoform contains protein kinase A (PKA) phosphorylation sites within the S2 binding site that are absent in skeletal muscle isoforms. Although phosphorylating these residues abolishes binding to myosin S2,⁴ the functional role of this phosphorylation is not well understood. Stelzer et al³ examined the effect of PKA on stretch activation in skinned cardiac myocytes of wildtype and cMyBP-C KO mice. Their findings provide an important piece of the puzzle—cMyBP-C slows crossbridge cycling kinetics (confirming earlier results⁵) and, importantly, this effect can be relieved by PKA-based phosphorylation of cMyBP-C.

It is well known from work initiated by Professor Pringle mid last century that stretch activation is most pronounced in asynchronous flight muscle, where it gives rise to wing beat frequencies that far exceed the capacity of the sarcoplasmic reticulum to activate and relax myofilaments.⁶ . . . [Full Text of this Article]

Related Article:

Protein Kinase A–Mediated Acceleration of the Stretch Activation Response in Murine Skinned Myocardium Is Eliminated by Ablation of cMyBP-C

Julian E. Stelzer, Jitandrakumar R. Patel, and Richard L. Moss
Circ. Res. 2006 99: 884-890. [Abstract] [Full Text] [PDF]

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