Isometric Tension and Mutant Myosin Heavy Chain Content in Single Skeletal Myofibers from Hypertrophic Cardiomyopathy Patients

Several mutations in theβ-myosin heavy chain (β-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 mutantβ-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→Glnmutation, the mutantβ-MHC comprises 47.3±9.1% of the totalβ-MHC present in single slow-twitch fibers. Therefore, both alleles of theβ-MHC gene are on average equally expressed. Isometric tension was decreased by 18% in slow fibers from HCM patients with the 403Arg→Glnmutation, but was unchanged in slow fibers from patients with two otherβ-MHC gene mutations. Taken together with the previous demonstration of reduced velocities generated by these myosins in anin vitroassay, our results suggest that the mutantβ-myosins are functional molecular motors that are able to generate tension and movement, but with abnormal kinetics.