Altered Contractility of Skeletal Muscle in Mice Deficient in Titin’s M-Band Region |
| |
Authors: | Coen AC Ottenheijm Katharina Rost Henk Granzier |
| |
Institution: | 1 Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ 85724, USA 2 Neuromuscular and Cardiovascular Cell Biology, Max-Delbruck Center for Molecular Medicine, 13125 Berlin, Germany |
| |
Abstract: | We investigated the contractile phenotype of skeletal muscle deficient in exons MEx1 and MEx2 (KO) of the titin M-band by using the cre-lox recombination system and a multidisciplinary physiological approach to study skeletal muscle contractile performance. At a maximal tetanic stimulation frequency, intact KO extensor digitorum longus muscle was able to produce wild-type levels of force. However, at submaximal stimulation frequency, force was reduced in KO mice, giving rise to a rightward shift of the force-frequency curve. This rightward shift of the force-frequency curve could not be explained by altered sarcoplasmic reticulum Ca2+ handling, as indicated by analysis of Ca2+ transients in intact myofibers and expression of Ca2+-handling proteins, but can be explained by the reduced myofilament Ca2+ sensitivity of force generation that we found. Western blotting experiments suggested that the excision of titin exons MEx1 and MEx2 did not result in major changes in expression of titin M-band binding proteins or phosphorylation level of the thin-filament regulatory proteins, but rather in a shift toward expression of slow isoforms of the thick-filament-associated protein, myosin binding protein-C. Extraction of myosin binding protein-C from skinned muscle normalized myofilament Ca2+ sensitivity of the KO extensor digitorum longus muscle. Thus, our data suggest that the M-band region of titin affects the expression of genes involved in the regulation of skeletal muscle contraction. |
| |
Keywords: | LV left ventricle EDL extensor digitorum longus MURF-1 muscle-specific ring finger protein-1 FHL2 four-and-a-half LIM protein-2 SR sarcoplasmic reticulum Tm tropomyosin CSA cross-sectional area MHC myosin heavy chain MRLC myosin regulatory light chain MyBP-C myosin binding protein C SERCA sarcoplasmic reticulum calcium ATPase |
本文献已被 ScienceDirect 等数据库收录! |
|