Role of cellular Na+ accumulation in acetylcholine-induced desensitization of guinea pig ileal longitudinal muscle.

The role of cellular Na+ accumulation in acetylcholine-induced desensitization was investigated in guinea pig ileal longitudinal muscle. Desensitization was induced by the pretreatment with acetylcholine (10(-4) M, 30 min) and was expressed by the rightward shift in the concentration-response curve for acetylcholine after the treatment. The same treatment with acetylcholine caused accumulation of cellular Na+ that amounted to about 3.5-fold of the control level. To study the relationship between the gain of cellular Na+ and the development of desensitization, we treated the muscle strips with acetylcholine under the condition 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 lowest level when acetylcholine induced no increase in cellular Na+, while desensitization developed in proportion to the increase in cellular Na+ content. However, when cellular Na+ was increased by another method (by the treatment with ouabain), the inhibition of the acetylcholine response was far less than that observed in the case of desensitization. We concluded that both muscarinic stimulation and the accompanying accumulation of cellular Na+ are required for desensitization to occur in full. This desensitization could be the result of a muscarinic stimulated and cellular Na+-dependent mechanism.