SEROTONERGIC MODULATION OF MUSCLE ACETYLCHOLINE-RECEPTORS OF DIFFERENT SUBUNIT COMPOSITION

Modulation of muscle acetylcholine (AcCho) receptors (AcChoRs) by sero tonin [5-hydroxytryptamine (5HT)] and other serotonergic compounds was studied in Xenopus laevis oocytes. Various combinations of alpha, bet a, gamma, and delta subunit RNAs were injected into oocytes, and membr ane currents elicited by AcCho were recorded under voltage clamp. Judg ing by the amplitudes of AcCho currents generated, the levels of funct ional receptor expression were: alpha beta gamma delta > alpha beta de lta > alpha beta gamma > alpha gamma delta. The alpha beta gamma delta and alpha beta delta AcChoR subtypes were strongly blocked by 5HT, wh ereas the alpha beta gamma receptor was blocked only slightly. The ord er of blocking potency of AcChoRs by 5HT was: alpha beta delta > alpha beta gamma delta > alpha beta gamma. 5HT receptor antagonists, such a s methysergide and spiperone, sere even more potent blockers of AcChoR s than 5HT but did not show much subunit selectivity. Blockage of alph a beta gamma delta and alpha beta delta receptors by 5HT was voltage-d ependent, and the voltage dependence was abolished when the delta subu nit was omitted. These findings may need to be taken into consideratio n when trying to elucidate the mode of action of many clinically impor tant serotonergic compounds.