Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics
| Autor: | Julian E. Stelzer, Matthew R. Locher, Maria V. Razumova, Jitandrakumar R. Patel, Holly S. Norman, Richard L. Moss |
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| Rok vydání: | 2009 |
| Předmět: |
Gene isoform
Physiology chemical and pharmacologic phenomena Myosins Biology Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Isomerism Myofibrils In vivo Isometric Contraction Physiology (medical) Myosin Animals Myocyte Myocytes Cardiac Calcium Signaling Pyruvates Calcium signaling Adenosine Triphosphatases Models Statistical Myosin Heavy Chains Myocardium Articles Myocardial Contraction Rats Cell biology Adenosine Diphosphate Kinetics Adenosine diphosphate chemistry Biochemistry Thyroidectomy Female Cardiology and Cardiovascular Medicine Myofibril Adenosine triphosphate |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 297:H247-H256 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | The ventricles of small mammals express mostly α-myosin heavy chain (α-MHC), a fast isoform, whereas the ventricles of large mammals, including humans, express ∼10% α-MHC on a predominately β-MHC (slow isoform) background. In failing human ventricles, the amount of α-MHC is dramatically reduced, leading to the hypothesis that even small amounts of α-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 ( fapp) and detachment ( gapp) for myosins composed of 100% α-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% α-MHC or 100% β-MHC were used to measure ATPase activity, isometric force, and the rate constant of force redevelopment ( ktr) in solutions of varying Ca2+concentrations. The rate of ATP utilization was ∼2.5-fold higher in preparations expressing 100% α-MHC compared with those expressing only β-MHC, whereas ktrwas 2-fold faster in the α-MHC myocardium. From these variables, we calculated fappto be approximately threefold higher for α-MHC than β-MHC and gappto be twofold higher in α-MHC. Mathematical modeling of isometric twitches predicted that small increases in α-MHC significantly increased the rate of force development. These results suggest that low-level expression of α-MHC has significant effects on contraction kinetics. |
| Databáze: | OpenAIRE |
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