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- W4232783263 abstract "Cardiac myosin binding protein C (cMyBP-C) is a sarcomeric protein involved in the regulation of cardiac muscle contraction. Effects of cMyBP-C on contraction are thought to be mediated in part by limiting the interactions of actin and myosin to slow myocyte shortening velocity and power output. Although interactions with myosin S2 on the thick filament have been proposed as a way in which cMyBP-C could limit shortening velocity (e.g., by creating a drag force on myosin heads), interactions of cMyBP-C with actin could also account for slowed shortening velocity. For instance, cMyBP-C could create a drag that opposes filament sliding by transiently linking thick and thin filaments together. To explore this possibility we created transgenic mice that express a mutant cMyBP-C with a point mutation, L348P (human L352P), located in a conserved sequence within the regulatory M-domain that increases cMyBP-C binding to actin in vitro. We reasoned that if the mutation also enhanced binding to actin in sarcomeres then shortening velocity would be slowed in myocytes from L348P mice. Results show that transgenic mice expressing the L348P mutation are viable and that L348P cMyBP-C is expressed in sarcomeres. Permeabilized myocytes from transgenic mice showed altered force production including reduced maximal force and enhanced calcium sensitivity of tension. Shortening velocity and power output were significantly reduced whereas passive stiffness and myocyte visco-elasticity were significantly increased. Together these data are consistent with the idea that cMyBP-C creates an internal load in the sarcomere by binding to actin." @default.
- W4232783263 created "2022-05-12" @default.
- W4232783263 creator A5030915178 @default.
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- W4232783263 date "2014-07-18" @default.
- W4232783263 modified "2023-09-30" @default.
- W4232783263 title "Abstract 93: A Gain-of-Function Mutation in Cardiac Myosin Binding Protein-C Increases Viscoelastic Load and Slows Shortening Velocity in Myocytes from Transgenic Mice" @default.
- W4232783263 doi "https://doi.org/10.1161/res.115.suppl_1.93" @default.
- W4232783263 hasPublicationYear "2014" @default.
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