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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/H247    most recent 00922.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Locher, M. R. Articles by Moss, R. L. PubMed PubMed Citation Articles by Locher, M. R. Articles by Moss, R. L.

Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics

¹Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; and ²Department of Bioengineering, University of Washington, Seattle, Washington

Submitted 21 August 2008 ; accepted in final form 14 April 2009

The ventricles of small mammals express mostly -myosin heavy chain (-MHC), a fast isoform, whereas the ventricles of large mammals, including humans, express 10% -MHC on a predominately β-MHC (slow isoform) background. In failing human ventricles, the amount of -MHC is dramatically reduced, leading to the hypothesis that even small amounts of -MHC on a predominately β-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% -MHC or β-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% -MHC or 100% β-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 2.5-fold higher in preparations expressing 100% -MHC compared with those expressing only β-MHC, whereas k_tr was 2-fold faster in the -MHC myocardium. From these variables, we calculated f_app to be approximately threefold higher for -MHC than β-MHC and g_app to be twofold higher in -MHC. Mathematical modeling of isometric twitches predicted that small increases in -MHC significantly increased the rate of force development. These results suggest that low-level expression of -MHC has significant effects on contraction kinetics.

-myosin heavy chain; rate constants of cross-bridge attachment and detachment; rate of rise of force