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Altered contractility of skeletal muscle in mice deficient in titin's M-band region

Item Type:Article
Title:Altered contractility of skeletal muscle in mice deficient in titin's M-band region
Creators Name:Ottenheijm, C.A. and Hidalgo, C. and Rost, K. and Gotthardt, M. and Granzier, H.
Abstract:We investigated the contractile phenotype of skeletal muscle deficient in the titin's M-band exons MEx1 and MEx2 (KO) 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 EDL muscle was able to produce wildtype 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 Ca(2+)handling as indicated by analysis of Ca(2+)transients in intact myofibers and expression of Ca(2+)handling proteins, but can be explained by the reduced myofilament Ca(2+)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 towards expression of slow isoforms of the thick filament-associated protein myosin binding protein-C (MyBP-C). Extraction of MyBP-C from skinned muscle normalized myofilament Ca(2+)sensitivity of KO EDL 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:Titin, M-Band, Skeletal Muscle, Ca(2+) Sensitivity, Animals, Mice
Source:Journal of Molecular Biology
ISSN:0022-2836
Publisher:Elsevier (The Netherlands)
Volume:393
Number:1
Page Range:10-26
Date:16 October 2009
Official Publication:https://doi.org/10.1016/j.jmb.2009.08.009
PubMed:View item in PubMed

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