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

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/P_o · 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/P_o · ML/sec) during half-maximal Ca²⁺ activations. There was also an effect on the rate constant of force redevelopment (k_tr) during half-maximal Ca²⁺ activations, with k_tr 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.