Neurotrophic regulation of two properties of skeletal muscle by impulse-dependent and spontaneous acetylcholine transmission

Daniel B. Drachman, Elis F. Stanley, Alan Pestronk, John W. Griffin, Donald L. Price

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we have evaluated the role of impulse-dependent and spontaneous acetylcholine (ACh) transmission in the neural regulation of two muscle properties: the resting membrane potential (RMPF) and the number of extrajunctional ACh receptors. Complete blockade of ACh transmission was produced by infusion of α-bungarotoxin (α-BuTx) into the soleus muscles of rats in vivo via implanted osmotic pumps. Blockade of nerve impulse conduction was induced by prolonged treatment of the sciatic nerves of rats with tetrodotoxin (TTX). Control studies demonstrated that the pharmacological actions of α-BuTx and TTX were highly specific, with no significant impairment of fast axonal transport or alterations in the morphology or physiology of the treated nerves. ACh blockade using α-BuTx produced a fall in the RMP that was identical to the effect of surgical denervation with respect to the time of onset rate of development, and extent of change. Blockade of nerve impulses using TTX produced a similar but partial change in the RMP that began later and progressed more slowly than that of denervation. Similarly, the increase of extrajunctional ACh receptors following α-BuTx-induced blockade of ACh transmission was identical to that of surgical denervation. By contrast, the effect of nerve impulse block using TTX was less pronounced at equivalent time points. Our findings indicate that specific pharmacological blockade of ACh transmission produces changes in the RMP and extrajunctional ACh receptors of skeletal muscle that are quantitatively equivalent to those of denervation. This suggests that ACh transmission itself mediates the nerve's trophic regulation of those of denervation. This suggests that ACh transmission itself mediates the nerve's trophic regulation of these muscle properties. Impulse-related ACh release and/or the muscle usage that it triggers account for only part of the regulatory effect; spontaneous ACh transmission (quantal and/or nonquantal) contributes the remainder. We suggest that nonquantal ACh release may represent the neurotrophic influence not fully accounted for in previous studies.

Original languageEnglish (US)
Pages (from-to)232-243
Number of pages12
JournalUnknown Journal
Volume2
Issue number2
DOIs
StatePublished - 1982

ASJC Scopus subject areas

  • Neuroscience(all)

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