During early postnatal development, the contractile, fatigue and metabolic properties of the diaphragm may be different than those in the adult muscle due to the pattern of polyneuronal innervation of muscle fibers. Thus, the diaphragm in younger animals may be more susceptible to respiratory stresses. If either a diminished motor responsiveness or an abnormal development resulted in diaphragm fatigue, respiratory failure might result and contribute in conditions such as respiratory distress syndrome and sudden infant death syndrome. The objectives of the proposed research are to determine the developmental changes in: 1) The contractile and fatigue properties of the diaphragm; 2) the metabolic properties of diaphragm muscle fibers; and 3) the correlation between physiological and metabolic properties. The proposed studies will examine the control of the diaphragm of kittens during the first 3 weeks of postnatal development. This period corresponds with the disappearance of polyneuronal innervation in the diaphragm. The contractile and fatigue properties of the whole diaphragm will be studied using an in vitro muscle strip preparation. In an in vivo preparation, single diaphragm motor units will be isolated in anesthetized kittens by stimulation of dissected ventral root filaments of the phrenic nerve. In both preparations, the contractile properties to be studied will include: 1) Contraction time; 2) Half relaxation time; and 3) Force/frequency relationships. Fatigue will be assessed using a standard fatigue test. The metabolic properties of individual muscle fibers in the diaphragm will be determined by quantifying the histochemical reactions for: 1) Succinate dehydrogenase (SDH), and oxidative enzyme; 2) Alpha-Glycerophosphate dehydrogenase (GPD), a glycolytic enzyme; and 3) Myosin adenosine triphophatase (ATPase), an enzyme involved in the hydrolysis of ATP. This quantitative analysis of histochemical reactions will utilize a photometric technique implemented on a computer-based image processing system. In population studies, the mean SDH, GPD and ATPase activities will be compared statistically with contractile and fatigue properties of the whole muscle at different ages. In motor unit studies, the constituent muscle fibers of a unit will be identified using the method of glycogen depletion, where motor unit fibers are depleted of glycogen by repeated activation. The SDH, GPD and myosin ATPase activities of these unit fibers will then be compared with those of fibers not belonging to the unit. The correlations between motor unit contractile and fatigue properties and the metabolic properties of muscle fibers belonging to the motor unit will be determined.
| Greising, Sarah M; Gransee, Heather M; Mantilla, Carlos B et al. (2012) Systems biology of skeletal muscle: fiber type as an organizing principle. Wiley Interdiscip Rev Syst Biol Med 4:457-73 |
| 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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