Effect of cardiac myosin binding protein-C on mechanoenergetics in mouse myocardium

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/t_PTU) 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/t_PTU. 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/t_PTU (26.1±2.6%) compared with +/+_PTU (17.1±1.6%). In skinned myocardial strips, maximum isometric tension was similar in t/t _PTU (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/t_PTU (7.31±1.17 Hz) compared with +/+ _PTU (4.48±0.60 Hz) and was significantly more sensitive to phosphate concentration in the t/t_PTU. Under rigor conditions, the internal viscous load was significantly lower in the t/t_PTU compared with +/+_PTU, ie, ≈40% lower at 1 Hz. These results collectively suggest that contractile efficiency is enhanced in the t/t_PTU, 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.