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- W1992084236 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/d t 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." @default.
- W1992084236 created "2016-06-24" @default.
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- W1992084236 date "2011-03-01" @default.
- W1992084236 modified "2023-10-03" @default.
- W1992084236 title "Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium" @default.
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- W1992084236 doi "https://doi.org/10.1152/ajpheart.00452.2010" @default.
- W1992084236 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3064314" @default.
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