Loaded Shortening, Power Output, and Rate of Force Redevelopment Are Increased With Knockout of Cardiac Myosin Binding Protein-C

F. Steven Korte, Kerry S. McDonald, Samantha P. Harris, Richard L. Moss

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Myosin binding protein-C (MyBP-C) is localized to the thick filaments of striated muscle where it appears to have both structural and regulatory functions. Importantly, mutations in the cardiac MyBP-C gene are associated with familial hypertrophic cardiomyopathy. The purpose of this study was to examine the role that MyBP-C plays in regulating force, power output, and force development rates in cardiac myocytes. Skinned cardiac myocytes from wild-type (WT) and MyBP-C knockout (MyBP-C-/-) mice were attached between a force transducer and position motor. Force, loaded shortening velocities, and rates of force redevelopment were measured during both maximal and half-maximal Ca2+ activations. Isometric force was not different between the two groups with force being 17.0±7.2 and 20.5±3.1 kN/m2 in wild-type and MyBP-C-/- myocytes, respectively. Peak normalized power output was significantly increased by 26% in MyBP-C-/- myocytes (0.15±0.01 versus 0.19±0.03 P/Po · ML/sec) during maximal Ca2+ activations. Interestingly, peak power output in MyBP-C-/- myocytes was increased to an even greater extent (46%, 0.09±0.03 versus 0.14±0.02 P/Po · ML/sec) during half-maximal Ca2+ activations. There was also an effect on the rate constant of force redevelopment (ktr) during half-maximal Ca2+ activations, with ktr being significantly greater in MyBP-C-/- myocytes (WT=5.8±0.9 s-1 versus MyBP-C-=7.7±1.7 s-1). These results suggest that cMyBP-C is an important regulator of myocardial work capacity whereby MyBP-C acts to limit power output.

Original languageEnglish (US)
Pages (from-to)752-758
Number of pages7
JournalCirculation Research
Volume93
Issue number8
DOIs
StatePublished - Oct 17 2003
Externally publishedYes

Keywords

  • Cardiac contractility
  • Cardiac myocytes
  • Myosin binding protein-C
  • Power output
  • Sarcomere proteins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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