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1 University of Wisconsin Medical School
2 University of Washington - Seattle
3 Case Western Reserve University
* To whom correspondence should be addressed. E-mail: locher{at}physiology.wisc.edu.
The ventricles of small mammals express mostly
MHC, a fast isoform, while the ventricles of large mammals including humans express ~10%
MHC on a predominately
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
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 (fapp) and detachment (gapp) for myosins comprised of 100%
or
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%
MHC were used to measure ATPase activity, isometric force, and the rate constant of force redevelopment (ktr) in solutions of varying [Ca2+]. The rate of ATP utilization was approximately 2.5-fold higher in preparations expressing 100%
MHC compared to those expressing only
MHC, while ktr was 2-fold faster in
MHC myocardium. From these variables, we calculated fapp to be approximately 3-fold higher for
than
MHC, and gapp to be 2-fold higher in
MHC. Mathematical modeling of isometric twitches predicted that small increases in
MHC significantly increased the rate of force development (dF/dtmax). These results suggest that low-level expression of
MHC has significant effects on contraction kinetics.
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