Abstract
We have studied the role of the highly conserved residue alphaLysine145 in the early steps of activation by acetylcholine of the nicotinic acetylcholine receptor (nAChR). Both macroscopic and single-channel currents were recorded in the slowly desensitizing chimeric mutant receptor alpha7V201-5HT3A/R432Q/R436D/R440A, made of alpha7 nAChRs and serotonin receptors of subtype 3A (ch1), and its corresponding mutant K145A (ch1/K145A) expressed in Xenopus oocytes. Mutant ch1/K145A receptors had a reduced gating function similar to that produced by the same mutation in the wild type receptor alpha7. The mutated receptor has reduced opening rate constants, beta, and increased closing rate constants, alpha.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / pharmacology
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Animals
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Azocines / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Carbachol / pharmacology
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Cattle
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Cholinergic Agonists / pharmacology
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Models, Biological
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Nicotine / pharmacology
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Patch-Clamp Techniques
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Protein Binding
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Pyridines / pharmacology
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Quinolizines / pharmacology
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Receptors, Nicotinic / drug effects
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Receptors, Nicotinic / metabolism*
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Receptors, Nicotinic / physiology
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Receptors, Serotonin, 5-HT3 / metabolism*
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Recombinant Fusion Proteins / agonists
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Recombinant Fusion Proteins / metabolism*
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Recombinant Fusion Proteins / physiology
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Serotonin 5-HT3 Receptor Agonists
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Xenopus
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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Alkaloids
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Azocines
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Bridged Bicyclo Compounds, Heterocyclic
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Cholinergic Agonists
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Pyridines
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Quinolizines
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Receptors, Nicotinic
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Receptors, Serotonin, 5-HT3
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Recombinant Fusion Proteins
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Serotonin 5-HT3 Receptor Agonists
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alpha7 Nicotinic Acetylcholine Receptor
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cytisine
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Nicotine
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Carbachol
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epibatidine