For the past six 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 in nerves and muscle. In parallel to these experiments, we have developed mathematical models that relate the biomagnetic field to cellular action currents, with the major conclusion that the magnetic recording technique provides, within limits that we now understand in detail, better quantitative information about the electrophysiology of active nerve and muscle cells than the conventional extracellular electric measurements. A quantitatively-accurate measure of the intracellular action currents and the transmembrane action potential generated by these currents can even be obtained magnetically without penetrating the cell membrane, avoiding the membrane damage caused by conventional micropipettes. The technique also provides a direct measurement of intracellular conductivity, as we recently demonstrated for a single giant axons in the crayfish and earthworm. We propose to utilize the advantages of magnetic techniques to study the electrophysiology of skeletal muscle. First we will conduct a series of measurements of electric and magnetic signals from single motor units in exposed animal muscles to establish, by means of our mathematical models, a firm theoretical description of the relationship in muscle between the magnetically-recorded action current and the electrically-recorded intracellular and extracellular action potentials, and to determine effective electrical conductivities for muscle fiber bundles. These results should provide us with basic knowledge that will ultimately aid in understanding both conventional EMG recordings and non-invasive magnetic recordings from skeletal muscle in humans. The quantitative features and simplicity of magnetic measurements make the magnetic recording technique highly appropriate for monitoring of possible different physiological stages in the development of muscular diseases. We will test this by invasive recordings on the hind-limb muscles from a mouse model of muscular dystrophy. These experiments should help identify possible characteristic electrophysiological differences between healthy and diseased muscle, and may provide physiological time thresholds for drug therapies in muscular and neuromuscular diseases. Finally, we will evaluate our magnetic technique as a totally non-invasive measurement of the time-course of muscular disease. We will examine the effects of restricted muscle use and its recently reported possible inhibition of muscular dystrophy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024751-02
Application #
3409615
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-03-01
Project End
1990-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
2
Fiscal Year
1988
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
37203
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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