Effect of Cardiac Myosin Binding Protein-C on Mechanoenergetics in Mouse Myocardium

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Abstract

Abstract—

We examined the effect of cardiac myosin binding protein-C (cMyBP-C) on contractile efficiency in isovolumically contracting left ventricle (LV) and on internal viscosity and oscillatory work production in skinned myocardial strips. A 6-week diet of 0.15% 6-n-propyl-2-thiouracil (PTU) was fed to wild-type (+/+PTU) and homozygous-truncated cMyBP-C (t/tPTU) mice starting at age ≈8 weeks and leading to a myosin heavy chain (MHC) isoform profile of 10% α-MHC and 90% β-MHC in both groups. Western blot analysis confirmed that cMyBP-C was present in the +/+PTU and effectively absent in the t/tPTU. Total LV mechanical energy per beat was quantified as pressure-volume area (PVA). O2 consumption (VO2) per beat was plotted against PVA at varying LV volumes. The reciprocal of the slope of the linear VO2–PVA relation represents the contractile efficiency of converting O2 to mechanical energy. Contractile efficiency was significantly enhanced in t/tPTU (26.1±2.6%) compared with +/+PTU (17.1±1.6%). In skinned myocardial strips, maximum isometric tension was similar in t/tPTU (18.7±2.1 mN · mm−2) and +/+PTU (21.9±4.0 mN · mm−2), but maximum oscillatory work induced by sinusoidal length perturbations occurred at higher frequencies in t/tPTU (7.31±1.17 Hz) compared with +/+PTU (4.48±0.60 Hz) and was significantly more sensitive to phosphate concentration in the t/tPTU. Under rigor conditions, the internal viscous load was significantly lower in the t/tPTU compared with +/+PTU, ie, ≈40% lower at 1 Hz. These results collectively suggest that contractile efficiency is enhanced in the t/tPTU, probably through a reduced loss of mechanical energy by a viscous load normally provided by cMyBP-C and through a gain of phosphate-dependent oscillatory work normally inhibited by cMyBP-C.

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