Fluctuation of Acetylcholine Sensitivity in Skeletal Muscles with Development, Denervation and Glycerol Treatment

Abstract

The variation of acetylcholine (ACh) sensitivity induced by development, denervation and glycerol treatment was studied using skeletal muscles of frogs and rats. In the course of metamorphosis from tadpole to adult, sensitivities (affinity) of rectus abdominis muscles of frogs to ACh and n-butyltrimethylammonium (BTMA) increased, as did the maximum responses (intrinsic activity) to BTMA, whereas the sensitivities to ACh-competitive antagonist decreased. The increasing phenomena were similar to the supersensitivity seen with denervation. The slope of dose-inhibitory response curve for curare-like agents changed from 1.0 to 1.5 with development of muscles. These results suggest changes in ACh receptors. With 4 or 10% glycerol treatment of chronically denervated diaphragm muscles, the responses to ACh decreased, whereas those to ATP increased. The maximum responses and sensitivity of ACh dose-response curves on glycerinated muscles decreased dose dependently with glycerol. ACh log dose-response curves of muscles treated with 2 % glycerol shifted in parallel with d-tubocurarine application and pA2 values were observed to be similar to those of non-treated muscles. The responses of glycerinated muscles to ACh were potentiated by 1.5 µM neostigmine less than those seen in non-treated muscles. The increase in ACh sensitivity with development may be in close analogy to the supersensitivity seen with denervation, and the pattern of the increase in ACh sensitivity seen with development or denervation was the reverse of that seen with glycerol treatment. The sensitivity of ACh receptor is probably closely related with the glycerol treatment.