| First Author | Ottenheijm CA | Year | 2009 |
| Journal | J Mol Biol | Volume | 393 |
| Issue | 1 | Pages | 10-26 |
| PubMed ID | 19683008 | Mgi Jnum | J:302904 |
| Mgi Id | MGI:6510917 | Doi | 10.1016/j.jmb.2009.08.009 |
| Citation | Ottenheijm CA, et al. (2009) Altered contractility of skeletal muscle in mice deficient in titin's M-band region. J Mol Biol 393(1):10-26 |
| abstractText | 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 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 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 Ca(2+) 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. |
