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

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/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/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.