EXPERIMENTAL NEUROLOGY 81,6 13-626 ( 1983) Rapid Decline in Acetylcholine Release and Content of Rat Extensor Digitorum Longus Muscle after Denervation DIANA CARDLINDEN,MICHAELW.NEWTON, ALAN D. GRINNELL, AND DONALD J. JENDEN’ Department of Biology, Occidental College, Los Angeles, California 90041, and Departments of Pharmacology and Physiology, School of Medicine, University of California, Los Angeles, California 90024 Received December IO, 1982; revised April 27, 1983 The amount of acetylcholine (ACh) and choline (Ch) in normal and denervated rat extensor digitorum longus (EDL) muscles, as well as that released spontaneously from these muscles, was determined by an extremely sensitive gas chromatographic- mass spectrometric assay method. We found decreasesin ACh content and spontaneous, resting ACh release as early as 8 h after denervation. The ACh content decreased to a plateau of 30% of control by 11 h; ACh release attained a plateau of 50% of control several hours later. These results showed that in denervated EDL muscles ACh content and spontaneous release (measured biochemicaily) decreased before nerve-evoked and spontaneous quantal release (measured physiologically) ceased at most synapses. The rapid reduction in ACh, or possibly in other substances that may be released with ACh, may be an important factor in initiating postsynaptic degenerative changes after nerve transection. Choline content and choline resting release increased significantly at both 1 and 3 days after nerve transection. These increases may be related to onset of postsynaptic neuromuscular degenerative changes. INTRODUCTION Muscle undergoes many changes as a result of transection of its motor axons (13, 40). As early as 3 h after nerve transection in the rat and mouse diaphragm (26, 46) and 17 h in denervated frog sartorius (19), the nerve terminals show disruption of mitochondria, vesicle clumping, and membrane Abbreviations: EDL-extensor digitorum longus, Ch-choline, ACh-acetylcholine, MEPP- miniature end-plate potential. ’ This work was supported by U.S. Public Health Service research grants MH-17691 (D.J.J.) and NSO6232 (A.D.G.) and a postdoctoral traineeship (NSO710) to D.C.L. We thank Dr. C. Gundersen for advice in early stages of the research. 613 0014-4886/83 $3.00 Copyright 0 1983 by Academic Press. Inc. All rights of reproduction in any form reserved