Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium
- 1 March 2011
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 300 (3), H869-H878
- https://doi.org/10.1152/ajpheart.00452.2010
Abstract
Myosin heavy chain (MHC) isoforms are principal determinants of work capacity in mammalian ventricular myocardium. The ventricles of large mammals including humans normally express ∼10% α-MHC on a predominantly β-MHC background, while in failing human ventricles α-MHC is virtually eliminated, suggesting that low-level α-MHC expression in normal myocardium can accelerate the kinetics of contraction and augment systolic function. To test this hypothesis in a model similar to human myocardium we determined composite rate constants of cross-bridge attachment ( fapp) and detachment ( gapp) in porcine myocardium expressing either 100% α-MHC or 100% β-MHC in order to predict the MHC isoform-specific effect on twitch kinetics. Right atrial (∼100% α-MHC) and left ventricular (∼100% β-MHC) tissue was used to measure myosin ATPase activity, isometric force, and the rate constant of force redevelopment ( ktr) in solutions of varying Ca2+concentration. The rate of ATP utilization and ktrwere approximately ninefold higher in atrial compared with ventricular myocardium, while tension cost was approximately eightfold greater in atrial myocardium. From these values, we calculated fappto be ∼10-fold higher in α- compared with β-MHC, while gappwas 8-fold higher in α-MHC. Mathematical modeling of an isometric twitch using these rate constants predicts that the expression of 10% α-MHC increases the maximal rate of rise of force (dF/d tmax) by 92% compared with 0% α-MHC. These results suggest that low-level expression of α-MHC significantly accelerates myocardial twitch kinetics, thereby enhancing systolic function in large mammalian myocardium.This publication has 52 references indexed in Scilit:
- Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kineticsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- Transmural variation in myosin heavy chain isoform expression modulates the timing of myocardial force generation in porcine left ventricleJournal Of Physiology-London, 2008
- Role of myosin heavy chain composition in the stretch activation response of rat myocardiumJournal Of Physiology-London, 2007
- β-Myosin heavy chain myocytes are more resistant to changes in power output induced by ischemic conditionsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006
- Power output is linearly related to MyHC content in rat skinned myocytes and isolated working heartsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2005
- Expression of cardiac troponin T with COOH-terminal truncation accelerates cross-bridge interaction kinetics in mouse myocardiumAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Kinetic Differences in Cardiac Myosins with Identical Loop 1 SequencesOnline Journal of Public Health Informatics, 2001
- Structural Mechanism of Muscle ContractionAnnual Review of Biochemistry, 1999
- The necessity of using two parameters to describe isotonic shortening velocity of muscle tissues: the effect of various interventions upon initial shortening velocity (vi) and curvature (b)Basic Research in Cardiology, 1986
- Energetic changes of myocardium as an adaptation to chronic hemodynamic overload and thyroid gland activityBasic Research in Cardiology, 1985