ROLE OF CELLULAR NA-INDUCED DESENSITIZATION OF GUINEA-PIG ILEAL LONGITUDINAL MUSCLE( ACCUMULATION IN ACETYLCHOLINE)

The role of cellular Na+ accumulation in acetylcholine-induced desensi tization was investigated in guinea pig ileal longitudinal muscle. Des ensitization was induced by the pretreatment with acetylcholine (10(-4 ) M, 30 min) and was expressed by the rightward shift in the concentra tion-response curve for acetylcholine after the treatment. The same tr eatment with acetylcholine caused accumulation of cellular Na+ that am ounted to about 3.5-fold of the control level. To study the relationsh ip between the gain of cellular Na+ and the development of desensitiza tion, we treated the muscle strips with acetylcholine under the condit ion in which the external Na+ concentration ranged from zero to 149.2 mM. The result showed that cellular Na+ content is closely related to the extent of desensitization; that is, desensitization was at the low est level when acetylcholine induced no increase in cellular Na+, whil e desensitization developed in proportion to the increase in cellular Na+ content. However, when cellular Na+ was increased by another metho d (by the treatment with ouabain), the inhibition of the acetylcholine response was far less than that observed in the case of desensitizati on. We concluded that both muscarinic stimulation and the accompanying accumulation of cellular Na+ are required for desensitization to occu r in full. This desensitization could be the result of a muscarinic st imulated and cellular Na+-dependent mechanism.