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Principal Investigator:
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Robert W. Wiseman, Ph.D.
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Organization:
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Michigan State University
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Project Ended:
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2004
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Dr. Robert Wiseman is investigating calcium handling and the energy required to pump these ions as a potential cause of the changes in muscle mass during spaceflight. Calcium ions trigger contraction and the mechanical response in muscle, and Dr. Wiseman believes they also signal longer-term changes in muscle gene expression. This research could lead to countermeasures to prevent muscle atrophy by manipulating muscle's capacity to pump calcium.
|
Principal Investigator:
|
Robert W. Wiseman, Ph.D.
|
|
Organization:
|
Michigan State University
|
|
Project Ended:
|
2004
|
Exposure of skeletal muscle to spaceflight results in a significant loss of mass and a shift in the phenotype from slow to fast muscle isoforms. To a limited extent, astronauts are able to ameliorate this remodeling of muscle tissue through exercise. If the mechanistic link between physiologic function and phenotype were better understood, design of countermeasures using combinations of exercise protocols and pharmaceuticals could be employed to increase the efficacy of training while on space missions.
We propose that altered physiologic function signals the initiation of the remodeling process through Ca+2-sensitive transcription factors (CSTFs), which are activated through changes in two homeostatic processes; mitochondrial ATP synthesis and sarcoplasmic reticulum (SR) ATPase Ca+2 handling. It is our assertion that alterations in phenotype in response to changes in load-bearing or any other metabolic stress involves processing information from the physiology in the form of feedback from these two homeostatic processes.
We use an integrative approach to study this problem in isolated superfused skeletal muscles using a combination of noninvasive techniques (31P-NMR and fluorescence spectroscopy and mechanics) and molecular techniques. In the first aim, we determine the sensitivity of cytosolic Ca+2 handling to metabolic loads induced by electrical pacing and metabolic inhibitors. In the second aim we test the response of CSTFs to alterations in Ca+2 homeostasis using ionophores, SR ATPase inhibitors, as well as the metabolic stresses we develop in aim 1. We believe that once the mechanistic link is established, we may be able to design countermeasures to mask the loss of mechanical loading by direct manipulation of cytosolic Ca+2 and more-effectively stave off the changes occurring in limb musculature.
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