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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024751-05
Application #
3409617
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-03-01
Project End
1993-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Parker, K K; Wikswo Jr, J P (1997) A model of the magnetic fields created by single motor unit compound action potentials in skeletal muscle. IEEE Trans Biomed Eng 44:948-57
Barach, J P (1996) Simulation calculations of cardiac virtual cathode effects. Comput Biomed Res 29:77-84
Barach, J P; Wikswo Jr, J P (1994) Magnetic fields from simulated cardiac action currents. IEEE Trans Biomed Eng 41:969-74
Wijesinghe, R S (1991) A mathematical model for calculating the vector magnetic field of a single muscle fiber. Math Biosci 103:245-74
Gielen, F L; Friedman, R N; Wikswo Jr, J P (1991) In vivo magnetic and electric recordings from nerve bundles and single motor units in mammalian skeletal muscle. Correlations with muscle force. J Gen Physiol 98:1043-61
Wikswo Jr, J P; van Egeraat, J M (1991) Cellular magnetic fields: fundamental and applied measurements on nerve axons, peripheral nerve bundles, and skeletal muscle. J Clin Neurophysiol 8:170-88
Wijesinghe, R S; Wikswo Jr, J P (1991) A model for compound action potentials and currents in a nerve bundle. II: A sensitivity analysis of model parameters for the forward and inverse calculations. Ann Biomed Eng 19:73-96
Wijesinghe, R S; Gielen, F L; Wikswo Jr, J P (1991) A model for compound action potentials and currents in a nerve bundle. I: The forward calculation. Ann Biomed Eng 19:43-72
Wijesinghe, R S; Gielen, F L; Wikswo Jr, J P (1991) A model for compound action potentials and currents in a nerve bundle. III: A comparison of the conduction velocity distributions calculated from compound action currents and potentials. Ann Biomed Eng 19:97-121
van Egeraat, J M; Friedman, R N; Wikswo Jr, J P (1990) Magnetic field of a single muscle fiber. First measurements and a core conductor model. Biophys J 57:663-7

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