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Date of Award

6-1988

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Dr. Alan J. McComas

Abstract

The studies that make up this thesis have been designed to describe and analyse the changes in muscle action potentials associated with muscular activity. The initial experiments were carried out in human muscle to examine changes in the muscle compound action potential (M-wave) during both stimulated and voluntary activity. It was found that the M-wave increased in amplitude either during or following either type of activity, and that this increase in M-wave amplitude could not be explained by either a movement artefact or a greater synchronization of action potential firing. It was hypothesized that the potentiation of the M-wave was due to a hyperpolarization of the muscle fibre membrane which was increasing the amplitude of the individual fibre action potentials. Experiments were then conducted on rat soleus muscle (in vivo) in order to measure changes in resting membrane and action potentials associated with contractile activity. After 5 min of intermittent tetanic stimulation at 20 Hz, the mean resting membrane potential increased from a baseline value of 79.5 ± 4.8 mV to a mean maximum of -92.6 ± 4.2 mV 3-6 min post-stimulation (p<.01). There was a corresponding increase in action potential amplitude; it rose from a resting value of 82.2 ± 10.8 mV to 98.1 ± 7.8 mV in the recovery period (p<.01). It was hypothesized that increased activity of the electrogenic Na⁺-K⁺ pump was causing the hyperpolarization. A series of experiments utilizing inhibitors of the Na⁺-K⁺ pump were then conducted; it was found that the administration of ouabain (1.25 x 10⁻⁴M), cooling the bathing medium (from 37°C to 19°C) or removal of extracellular K⁺ prevented the hyperpolarization following repetitive stimulation (p<.05). The magnitude of the electrogenic contribution of the Na⁺-K⁺ pump was then estimated by exposing stimulated muscle fibres to a high K⁺ (20 mM) medium. While in the control (unstimulated) condition this caused an immediate depolarization of the muscle fibre membrane to approximately -58 mV, stimulated fibres maintained membrane potentials of -79.5 mV (± 8.6 mV) for at least 3 min, which was approximately -30 mV greater than that predicted by the Goldman-Hodgkin-Katz (GHK) equation. It is concluded that the Na⁺-K⁺ pump plays an important role in maintaining muscle fibre excitability during muscular activity, which is additional to its role in the restoration and maintenance of ionic gradients for Na⁺ and K⁺. The temporary hyperpolarization of the muscle fibre membrane during increased Na⁺-K⁺ activity offers an explanation for the potentiation of muscle compound action potentials observed during voluntary and stimulated contractions.

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