MUSCLE ENERGY PROPERTIES SET STEADY STATE FUNCTION

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The long term objective of the applicant is to develop an in vivo non- invasive measure that is able to define the functional capacity for sustained activity of human skeletal muscle. The immediate goal is to acquire the necessary skills and knowledge in magnetic resonance spectroscopy experimentation and biochemistry to become a productive independent investigator in the area of cellular energetics. The UCHSC offers a unique environment. It has an established program involving tissue energetics and a Rehabilitation Medicine department whose faculty have a specific clinical interest in the peripheral motor control system and a goal to establish a research program in this area. Laurence Chan, M.D., Ph.D. is the sponsor for this award. Dr. Chan's experience and depth of involvement with in vivo magnetic resonance spectroscopy (MRS) experimentation and knowledge of MRS methodology and tissue energetics will be invaluable. Dr. Chan's sponsorship combined with the support demonstrated by the Department of Rehabilitation Medicine, and the UCHSC will create the foundation for a successful scientific academic career. Phase I: Dr. Chan and the advisory committee have created a two year Research Training Program for the applicant. During the training period the applicant will develop his knowledge in biochemistry and MRS experimentation through a rigorous program. The program includes didactic and independent studies, group seminar participation and computer modelling of cellular energetics. By the completion of the Phase I, the goal is to have a working differential equation based computer model of the energetic process occurring during stimulated isometric contractions within individual fibers with differing fiber-type characteristics. The technical skills and protocols for proton deoxymyoglobin spectroscopy and 31P MRS spectroscopy in the rat hindlimb and human musculature will be developed. Phase II: In the last three years, MRS will be utilized to establish that the skeletal muscle's energetic properties mechanistically determine the maximum steady-state function the muscle can achieve in both normal and pathological conditions. Hyper- and hypothyroid conditions will be used as a model to provide a wide spectrum of muscle energetic profiles in both human anterior tibialis and the rat hindlimb. These conditions will demonstrate the ability to define a spectrum of energetic states, and that both limbs of the energy balance need to be determined to uniquely define the energetics of skeletal muscle.