Reappearance of extrajunctional acetylcholine sensitivity in denervated rat muscle after blockage with α-bungarotoxin

Abstract

IN most vertebrate skeletal muscles only the endplate region of muscle membrane is sensitive to acetylcholine (ACh), but after denervation the entire extrajunctional membrane becomes sensitive^1,2. In rat diaphragm fibres the degree of extrajunctional ACh sensitivity increases steadily during the 7–9 d following denervation and then remains relatively constant at a high level for at least several weeks. It has been shown that this increase in ACh sensitivity results from the appearance of new ACh receptors in the extrasynaptic membrane^3,4, and an intriguing question is whether in already fully supersensitive fibres new ACh receptors continue to appear in the surface membrane. α-Bungarotoxin (α-BuTX) blocks the depolarising action of ACh on supersensitive muscle membrane⁴, and is thought to bind specifically and almost irreversibly to ACh receptors. Thus one can block all or most receptors of super-sensitive muscle fibres at a certain time. I report here experiments in which the reappearance of extrajunctional ACh sensitivity was followed after blocking sensitivity with α-BuTX, using denervated rat diaphragm muscle, maintained in organ culture⁵.