期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 297, 期 1, 页码 H247-H256出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00922.2008
关键词
alpha-myosin heavy chain; rate constants of cross-bridge attachment and detachment; rate of rise of force
资金
- National Heart, Lung, and Blood Institute [HL-61635]
Locher MR, Razumova MV, Stelzer JE, Norman HS, Patel JR, Moss RL. Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics. Am J Physiol Heart Circ Physiol 297: H247-H256, 2009. First published April 24, 2009; doi: 10.1152/ajpheart.00922.2008.-The ventricles of small mammals express mostly alpha-myosin heavy chain (alpha-MHC), a fast isoform, whereas the ventricles of large mammals, including humans, express similar to 10% alpha-MHC on a predominately beta-MHC (slow isoform) background. In failing human ventricles, the amount of alpha-MHC is dramatically reduced, leading to the hypothesis that even small amounts of alpha-MHC on a predominately beta-MHC background confer significantly higher rates of force development in healthy ventricles. To test this hypothesis, it is necessary to determine the fundamental rate constants of cross-bridge attachment (f(app)) and detachment (g(app)) for myosins composed of 100% alpha-MHC or beta-MHC, which can then be used to calculate twitch time courses for muscles expressing variable ratios of MHC isoforms. In the present study, rat skinned trabeculae expressing either 100% alpha-MHC or 100% beta-MHC were used to measure ATPase activity, isometric force, and the rate constant of force redevelopment (k(tr)) in solutions of varying Ca2+ concentrations. The rate of ATP utilization was similar to 2.5-fold higher in preparations expressing 100% alpha-MHC compared with those expressing only beta-MHC, whereas k(tr) was 2-fold faster in the alpha-MHC myocardium. From these variables, we calculated f(app) to be approximately threefold higher for alpha-MHC than beta-MHC and g(app) to be twofold higher in alpha-MHC. Mathematical modeling of isometric twitches predicted that small increases in alpha-MHC significantly increased the rate of force development. These results suggest that low-level expression of alpha-MHC has significant effects on contraction kinetics.
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