Effects of Cardiac Myosin Isoform Variation on Myofilament Function and Crossbridge Kinetics in Transgenic Rabbits
- 1 July 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation: Heart Failure
- Vol. 2 (4), 334-341
- https://doi.org/10.1161/circheartfailure.108.802298
Abstract
Background— The left ventricles of both rabbits and humans express predominantly β-myosin heavy chain (MHC). Transgenic (TG) rabbits expressing 40% α-MHC are protected against tachycardia-induced cardiomyopathy, but the normal amount of α-MHC expressed in humans is only 5% to 7% and its functional importance is questionable. This study was undertaken to identify a myofilament-based mechanism underlying tachycardia-induced cardiomyopathy protection and to extrapolate the impact of MHC isoform variation on myofilament function in human hearts. Methods and Results— Papillary muscle strips from TG rabbits expressing 40% (TG40) and 15% α-MHC (TG15) and from nontransgenic (NTG) controls expressing ≈100% β-MHC (NTG40 and NTG15) were demembranated and calcium activated. Myofilament tension and calcium sensitivity were similar in TGs and respective NTGs. Force-clamp measurements revealed ≈50% higher power production in TG40 versus NTG40 ( P P P Conclusions— The incorporation of 40% α-MHC leads to greater myofilament power production and more rapid crossbridge cycling, which facilitate ejection and relengthening during short cycle intervals, and thus protect against tachycardia-induced cardiomyopathy. Our results suggest, however, that, even when compared with the virtual absence of α-MHC in the failing heart, the 5% to 7% α-MHC content of the normal human heart has little if any functional significance.Keywords
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