Reduction of Denervation Supersensitivity of Muscle by Submechanical Threshold Stimulation

Abstract

IN normally innervated adult muscle, membrane sensitivity to acetylcholine (ACh) is localised to the endplate and tendon regions^1,2. After surgical denervation, this sensitivity spreads over the entire membrane surface reaching a peak within 5 to 7 d (ref. 3). Two hypotheses have been proposed to explain the restriction of ACh sensitivity in normally innervated muscle. The first suggests that a trophic substance is released from the motoneurone, restricting transmitter sensitivity to the end-plate region^4,5. The second hypothesis suggests that muscle ‘activity’ generates a self-feedback loop from the muscle onto the sarcolemma thus limiting ACh sensitivity to the neuro-muscular junction^3,6. Upon denervation, muscle ‘activity’ ceases and therefore the feedback loop is broken with the consequent loss of activity-mediated transmitter sensitivity restriction. Drachman and Witzke⁷ showed that direct electrical stimulation of the denervated rat diaphragm, resulting in contraction, suppressed the spread of ACh supersensitivity. Jones and Vrbová⁶ reported that chronic electrical stimulation of the extensor digitorum of rat, resulting in contractions, reduced supersensitivity to ACh subsequent to denervation.