Diversity of nicotinic receptors mediating Cl − current in Lymnaea neurons distinguished with specific agonists and antagonist

Diversity of nicotinic acetylcholine receptors (nAChRs) mediating Cl − current in voltage-clamped identifiable Lymnaea stagnalis neurons was studied using acetylcholine (ACh), three agonists and α-conotoxin ImI (ImI). Cytisine, nicotine, and choline, full agonists at α7 subunit-containing nAChRs of...

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Published in:	Neuroscience letters Vol. 373; no. 3; pp. 232 - 236
Main Authors:	Vulfius, C.A., Tumina, O.B., Kasheverov, I.E., Utkin, Yu.N., Tsetlin, V.I.
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier Ireland Ltd 20-01-2005 Elsevier
Subjects:	Acetylcholine Agonists Animals Chloride Channels - physiology Dose-Response Relationship, Drug Lymnaea - drug effects Lymnaea - physiology Lymnaea neurons Neurons - drug effects Neurons - physiology Nicotinic Agonists - pharmacology Nicotinic Antagonists - pharmacology Nicotinic receptors Receptors, Nicotinic - physiology α-Conotoxin ImI α7 subunit Agonists α7 subunit Acetylcholine Nicotinic receptors α-Conotoxin ImI Lymnaea neurons
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Summary:	Diversity of nicotinic acetylcholine receptors (nAChRs) mediating Cl − current in voltage-clamped identifiable Lymnaea stagnalis neurons was studied using acetylcholine (ACh), three agonists and α-conotoxin ImI (ImI). Cytisine, nicotine, and choline, full agonists at α7 subunit-containing nAChRs of vertebrates, were found to evoke at saturating concentration 84–92% of the maximal current elicited by ACh. ImI, known to block selectively α7 and α9 nAChRs, markedly diminished the responses to ACh. The average maximal ImI-induced block was 80%, leaving a residual current which had very slow kinetics. The choline-, cytisine-, and nicotine-induced currents were blocked by ImI almost completely, suggesting that they activate only ImI-sensitive receptors. Two groups of cells which differ in desensitization kinetics and in sensitivity to ImI were revealed. IC 50 values for ImI against ACh were 10.3 and 288 nM, respectively, with the rapidly desensitizing current being the more sensitive to ImI. The data obtained suggest the existence of at least three pharmacologically distinct subtypes of nicotinic receptors in Lymnaea neurons. Two of the subtypes are similar to α7 nAChRs of vertebrates, but differ from each other in their affinity for ImI and in their desensitization kinetics. The third subtype is quite distinct, in that it is resistant to ImI, is not activated by nicotine, cytisine or choline, and mediates a very slowly developing current.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-3940 1872-7972
DOI:	10.1016/j.neulet.2004.10.010