Altered Contractility of Skeletal Muscle in Mice Deficient in Titin's M-Band Region

JOURNAL OF MOLECULAR BIOLOGY

卷:393

Article

Ottenheijm, Coen A. C.¹  Hidalgo, Carlos¹  Rost, Katharina²  Gotthardt, Michael²  Granzier, Henk¹ 

[1] Univ Arizona, Dept Physiol, Sarver Mol Cardiovasc Res Program, Tucson, AZ 85724 USA

[2] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

关键词: titin;    M-band;    skeletal muscle;    Ca2+ sensitivity;   

DOI  :  10.1016/j.jmb.2009.08.009

来源: Elsevier

【 摘 要 】

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. (C) 2009 Published by Elsevier Ltd.

【 授权许可】

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