Ligand-gated ion channels opened by 5-HT in molluscan neurones.
1. 5-Hydroxytryptamine (5-HT) activated a fast (70 ms to half maximum) and desensitizing inward current through non-selective channels conducting predominantly monovalent cations in neurons 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-methyl-5-HT and arylbiguanides were ineffective (< 100 microM). 5-Methoxytryptamine which is inactive on vertebrate 5-HT3 receptors was a very weak agonist. 3. The responses were antagonized by the specific vertebrate 5-HT3 receptor blocker MDL-72222 (IC50 = 1 microM), but were only weakly affected by ondansetron (10 microM). The 5-HT2-type antagonist, ketanserin (< 5 microM) had no effect. The responses were also antagonized by the non-specific antagonists (+)-tubocurarine and strychnine. 4. Unitary currents through channels non-selective for monovalent cations, and with a conductance of 2pS, could be activated repeatedly by 5-HT or alpha-methyl-5-HT in outside-out patches from neurones exhibiting the fast 5-HT-activated current (I[5-HT]fast), even in the presence of 500 microM GDP-[beta S] in the recording pipette. This strongly supports direct-gating of these channels by 5-HT. The properties of these unitary currents resembled those of I[5-HT]fast. 5. The pharmacological properties of this molluscan 5-HT-operated, ligand-gated channel differed sufficiently from known vertebrate 5-HT3-type receptors to suggest that it represents a new class of 5-HT receptor.
School of Biological and Medical Sciences, St. Andrews, Fife.
K A
KA
Green
J J
JJ
Lambert
G A
GA
Cottrell
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006372:Helix, Snails; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007650:Ketanserin; D009474:Neurons / Q000187:drug effects; D017294:Ondansetron / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D003292:Convulsants; D007473:Ion Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D012701:Serotonin; D017294:Ondansetron; D007650:Ketanserin; D019204:GTP-Binding Proteins; D013331:Strychnine; C042253:bemesetron; D002118:Calcium