The objective of the proposed research is to study biomagnetic signals if single fiber and multicellular activity in skeletal muscle of normal animals, animal models of muscular plasticity, normal human subjects, and patients with certain muscular disorders. For the past three years, we have used our room-temperature, Biomagnetic-Current Probe to conduct a unique series of measurements of magnetic fields produced by cellular action currents (ACs) in muscle. In parallel, we have developed mathematical models that relate the biomagnetic field to cellular ACs, with the major conclusion that magnetic recording techniques provide, within limits that we now understand in detail, better quantitative information about the electrophysiology of active muscle cells that can be obtained with conventional extracellular electric recording. A quantitative measure of the intracellular ACs and the transmembrane action potential generated by these currents can even be obtained magnetically without penetrating the cell with micropipette. Alternatively, the magnetically-recorded AC combined with a microelectrode measurement of potential can provide the intracellular conductivity and membrane capacitance. We have measured electric and magnetic signals from whole muscles, single motor units, and single fibers from, mammalian muscles, enabling us to establish, by means of our mathematical models, a firm theoretical description of the relationship between the magnetically- recorded AC and the electrically-recorded intracellular and extracellular action potentials, and to determine effective electrical conductivities for muscle fiber bundles. We have also shown the relationship of ACs to contractile force. While it is imperative to continue adding to such basic knowledge, we now have sufficient information to assure a productive extension of our research to examine alterations of normal muscle membrane physiology. Technological advances have enabled us to obtained a unique, high-resolution Superconducting Quantum Interference Device (SQUID) magnetometer that is unsurpassed in its ability to noninvasively record the magnetomyogram (MMG). By applying all of our new magnetic recording techniques to study experimentally-induced alterations of muscle, we should be able to obtain new information on muscle plasticity, manifest under such conditions as disuse atrophy, work-induced hypertrophy, and denervation. By applying these new techniques to examine tissues of patients with muscular disorders, we should be able to begin elucidating mechanisms underlying muscle disease processes.
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