LIGAND-GATED ION CHANNELS OPENED BY 5-HT IN MOLLUSCAN NEURONS

1 5-Hydroxytryptamine (5-HT) activated a fast (70 ms to half maximum) and desensitizing inward current through non-selective channels conduc ting predominantly monovalent cations in neurones of Helix aspersa. 2 alpha-Methyl-5-HT was equipotent with 5-HT in activating this current, but the known selective agonists at vertebrate 5-HT3 receptors, 2-met hyl-5-HT and arylbiguanides were ineffective (<100 mu M). 5-Methoxytry ptamine which is inactive on vertebrate 5-HT3 receptors was a very wea k agonist. 3 The responses were antagonized by the specific vertebrate 5-HT3 receptor blocker MDL-72222 (IC50 = 1 mu M), but were only weakl y affected by ondansetron (10 mu M). The 5-HT2-type antagonist, ketans erin (<5 mu M), had no effect. The responses were also antagonized by the non-specific antagonists (+)-tubocurarine and strychnine. 4 Unitar y currents through channels non-selective for monovalent cations, and with a conductance of 2pS, could be activated repeatedly by 5-HT or al pha-methyl-5-HT in outside-out patches from neurones exhibiting the fa st 5-HT-activated current (I[5-HT](fast)), even in the presence of 500 mu M GDP-[beta S] in the recording pipette. This strongly supports di rect-gating of these channels by 5-HT. The properties of these unitary currents resembled those of I[5-HT](fast). 5 The pharmacological prop erties of this molluscan 5-HT-operated, ligand-gated channel differed sufficiently from known vertebrate 5-HT3-type receptors to suggest tha t it represents a new class of 5-HT receptor.