ACTION CURRENTS AND SKELETAL MUSCLE ELECTROPHYSIOLOGY

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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.