title: Effects of low-level &alpha;-myosin heavy chain expression on contractile kinetics in porcine myocardium.
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 (f(app)) and detachment (g(app)) 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 (k(tr)) in solutions of varying Ca(2+) concentration. The rate of ATP utilization and k(tr) were approximately ninefold higher in atrial compared with ventricular myocardium, while tension cost was approximately eightfold greater in atrial myocardium. From these values, we calculated f(app) to be ∼10-fold higher in α- compared with β-MHC, while g(app) was 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/dt(max)) 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.
authors.affiliation: 1Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53711, USA. locher@physiology.wisc.edu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Locher
authors.forename: Maria V
authors.initials: MV
authors.lastname: Razumova
authors.forename: Julian E
authors.initials: JE
authors.lastname: Stelzer
authors.forename: Holly S
authors.initials: HS
authors.lastname: Norman
authors.forename: Richard L
authors.initials: RL
authors.lastname: Moss
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D005260:Female; D006321:Heart / Q000502:physiology*; D008297:Male; D053580:Muscle Strength / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D013552:Swine / Q000502:physiology; D024723:Ventricular Myosins / Q000378:metabolism*
chemical_list: D024723:Ventricular Myosins; D018995:Myosin Heavy Chains; D009218:Myosins; D002118:Calcium