Isometric tension and mutant myosin heavy chain content in single skeletal myofibers from hypertrophic cardiomyopathy patients - PubMed (original) (raw)
Isometric tension and mutant myosin heavy chain content in single skeletal myofibers from hypertrophic cardiomyopathy patients
S Malinchik et al. J Mol Cell Cardiol. 1997 Feb.
Abstract
Several mutations in the beta-myosin heavy chain (beta-MHC) gene have been linked to hypertrophic cardiomyopathy (HCM). Because this gene is also expressed in slow-twitch fibers of skeletal muscle, we have been able to study the mutant beta-myosin content and mechanical properties associated with these myosin mutations in single skinned skeletal muscle fibers obtained from HCM patients. We found that in patients carrying the 403Arg-->Gln mutation, the mutant beta-MHC comprises 47.3 +/- 9.1% of the total beta-MHC present in single slow-twitch fibers. Therefore, both alleles of the beta-MHC gene are on average equally expressed. Isometric tension was decreased by 18% in slow fibers from HCM patients with the 403Arg-->Gln mutation, but was unchanged in slow fibers from patients with two other beta-MHC gene mutations. Taken together with the previous demonstration of reduced velocities generated by these myosins in an in vitro assay, our results suggest that the mutant beta-myosins are functional molecular motors that are able to generate tension and movement, but with abnormal kinetics.
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