This investigation will evaluate the underlying relationships between changes in myosin/troponin expression during development and specific morphological and functional characteristics of muscle fibers. In previous studies, the investigators found dramatic changes in myosin heavy chain isoforms, morphology and function in diaphragm fibers during development. This study will explore the relationships between these variables.
Specific aim 1 will determine the underlying basis for the postnatal establishment of morphological differences among diaphragm fibers. The hypothesis to be tested is that fiber type differences in postnatal growth reflect differences in synthesis rate of myosin heavy chain (MHC) isoforms that result in a higher MHC content of fibers expressing MHC2x and MHC2b isoforms compared to fibers expressing MHCslow and MHC2A isoforms.
Specific aim 2 will determine the underlying basis for the postnatal establishment of fiber type differences in maximum specific force (Po). The hypothesis to be tested is that postnatal increases in Po and adult fiber type difference in Po primarily reflect the influence of varying MHC content.
Specific Aim 3 will determine the underlying basis for the postnatal establishment of fiber type differences in Ca+2 sensitivity. The hypothesis to be tested is that fiber type differences in the dependence of force on myoplasmic Ca+2 relate to the expression of different troponin C isoforms; however within a single fiber, Ca+2 sensitivity is modulated by the extent of myosin light chain phosphorylation.
Specific Aim 4 will determine the underlying basis for the postnatal establishment of fiber type differences in actomyosin ATPase activity. The hypothesis to be tested is that fiber type differences in actomyosin ATPase activity reflect the combined influence of MHC content, the fraction of cross bridges in the force generating state (alpha-fs) and the apparent rate constant for cross bridge detachment (g-app). With shortening contractions, the increase in actomyosin ATPase activity varies across fiber types, reflecting differences in the impact of active shortening on alpha-fs and g-app.
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| Bukatina, Anna E; Sieck, Gary C; Campbell, Kenneth B et al. (2009) Characterization of secophalloidin-induced force loss in cardiac myofibrils. J Muscle Res Cell Motil 30:209-16 |
| Geiger, Paige C; Bailey, Jeffrey P; Mantilla, Carlos B et al. (2006) Mechanisms underlying myosin heavy chain expression during development of the rat diaphragm muscle. J Appl Physiol 101:1546-55 |
| Verheul, A Jeroen; Mantilla, Carlos B; Zhan, Wen-Zhi et al. (2004) Influence of corticosteroids on myonuclear domain size in the rat diaphragm muscle. J Appl Physiol 97:1715-22 |
| Mantilla, Carlos B; Zhan, Wen-Zhi; Sieck, Gary C (2004) Neurotrophins improve neuromuscular transmission in the adult rat diaphragm. Muscle Nerve 29:381-6 |
| Bukatina, Anna E; Sieck, Gary C (2003) Secophalloidin as a novel activator of skinned cardiac muscle. Biochem Biophys Res Commun 301:646-9 |
| Zhan, Wen-Zhi; Mantilla, Carlos B; Sieck, Gary C (2003) Regulation of neuromuscular transmission by neurotrophins. Sheng Li Xue Bao 55:617-24 |
| Geiger, Paige C; Bailey, Jeffrey P; Zhan, Wen-Zhi et al. (2003) Denervation-induced changes in myosin heavy chain expression in the rat diaphragm muscle. J Appl Physiol 95:611-9 |
| Han, Young-Soo; Geiger, Paige C; Cody, Mark J et al. (2003) ATP consumption rate per cross bridge depends on myosin heavy chain isoform. J Appl Physiol 94:2188-96 |
| Sieck, Gary C; Prakash, Y S; Han, Young-Soo et al. (2003) Changes in actomyosin ATP consumption rate in rat diaphragm muscle fibers during postnatal development. J Appl Physiol 94:1896-902 |
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