Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
1997 Sep 02;9418:9915-9. doi: 10.1073/pnas.94.18.9915.
Show Gene links
Show Anatomy links
Neuronal nicotinic threonine-for-leucine 247 alpha7 mutant receptors show different gating kinetics when activated by acetylcholine or by the noncompetitive agonist 5-hydroxytryptamine.
???displayArticle.abstract???
Mutation of the highly conserved leucine residue (Leu-247) converts 5-hydroxytryptamine (5HT) from an antagonist into an agonist of neuronal homomeric alpha7 nicotinic acetylcholine receptor expressed in Xenopus oocytes. We show here that acetylcholine (AcCho) activates two classes of single channels with conductances of 44 pS and 58 pS, similar to those activated by 5HT. However, the mean open time of AcCho-gated ion channels (11 ms) is briefer than that of 5HT-gated ion channels (18 ms). Furthermore, whereas the open time of AcCho channels lengthens with hyperpolarization, that of 5HT channels is decreased. In voltage-clamped oocytes, the apparent affinity of the alpha7 mutant receptor for 5HT is not modified by the presence of dihydro-beta-erythroidine, which acts on the AcCho binding site in a competitive manner. This indicates a noncompetitive action of 5HT on nicotinic acetylcholine receptors. Considered together, our findings show that AcCho gates alpha7 mutant channels with similar conductance but with different kinetic profile than the channels gated by 5HT, suggesting that the two agonists act on different docking sites. These results will help to understand the crosstalk between cholinergic and serotonergic systems in the central nervous system.
Auerbach,
Voltage dependence of mouse acetylcholine receptor gating: different charge movements in di-, mono- and unliganded receptors.
1996, Pubmed,
Xenbase
Auerbach,
Voltage dependence of mouse acetylcholine receptor gating: different charge movements in di-, mono- and unliganded receptors.
1996,
Pubmed
,
Xenbase
Bertrand,
Unconventional pharmacology of a neuronal nicotinic receptor mutated in the channel domain.
1992,
Pubmed
,
Xenbase
Bertrand,
Pharmacological properties of the homomeric alpha 7 receptor.
1992,
Pubmed
,
Xenbase
Chang,
Stoichiometry of a recombinant GABAA receptor.
1996,
Pubmed
,
Xenbase
Clark,
A direct comparison of the single-channel properties of synaptic and extrasynaptic NMDA receptors.
1997,
Pubmed
Colquhoun,
Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate.
1985,
Pubmed
Colquhoun,
Activation of ion channels in the frog end-plate by high concentrations of acetylcholine.
1988,
Pubmed
Couturier,
A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX.
1990,
Pubmed
,
Xenbase
Delbono,
Activation of the recombinant human alpha 7 nicotinic acetylcholine receptor significantly raises intracellular free calcium.
1997,
Pubmed
Filatov,
The role of conserved leucines in the M2 domain of the acetylcholine receptor in channel gating.
1995,
Pubmed
,
Xenbase
García-Colunga,
Blockage of muscle and neuronal nicotinic acetylcholine receptors by fluoxetine (Prozac).
1997,
Pubmed
,
Xenbase
García-Colunga,
Effects of serotonergic agents on neuronal nicotinic acetylcholine receptors.
1995,
Pubmed
,
Xenbase
García-Colunga,
Serotonergic modulation of muscle acetylcholine receptors of different subunit composition.
1996,
Pubmed
,
Xenbase
Kearney,
Determinants of nicotinic receptor gating in natural and unnatural side chain structures at the M2 9' position.
1996,
Pubmed
,
Xenbase
Labarca,
Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors.
1995,
Pubmed
,
Xenbase
McGehee,
Presynaptic ionotropic receptors.
1996,
Pubmed
Methfessel,
Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels.
1986,
Pubmed
,
Xenbase
Miledi,
A calcium-dependent transient outward current in Xenopus laevis oocytes.
1982,
Pubmed
,
Xenbase
Miledi,
Recording of single gamma-aminobutyrate- and acetylcholine-activated receptor channels translated by exogenous mRNA in Xenopus oocytes.
1983,
Pubmed
,
Xenbase
Mileo,
Protein kinase C modulates exogenous acetylcholine current in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Ortells,
Evolutionary history of the ligand-gated ion-channel superfamily of receptors.
1995,
Pubmed
Palma,
Neuronal nicotinic alpha 7 receptor expressed in Xenopus oocytes presents five putative binding sites for methyllycaconitine.
1996,
Pubmed
,
Xenbase
Palma,
Threonine-for-leucine mutation within domain M2 of the neuronal alpha(7) nicotinic receptor converts 5-hydroxytryptamine from antagonist to agonist.
1996,
Pubmed
,
Xenbase
Palma,
Co-expression of the neuronal alpha7 and L247T alpha7 mutant subunits yields hybrid nicotinic receptors with properties of both wild-type alpha7 and alpha7 mutant homomeric receptors.
1997,
Pubmed
,
Xenbase
Perry,
Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: possible index of early neuropathology.
1995,
Pubmed
Ragozzino,
Functional properties of neuronal nicotinic acetylcholine receptor channels expressed in transfected human cells.
1997,
Pubmed
Revah,
Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.
1991,
Pubmed
,
Xenbase
Séguéla,
Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium.
1993,
Pubmed
,
Xenbase
Sivilotti,
Recombinant nicotinic receptors, expressed in Xenopus oocytes, do not resemble native rat sympathetic ganglion receptors in single-channel behaviour.
1997,
Pubmed
,
Xenbase
Wonnacott,
Presynaptic nicotinic ACh receptors.
1997,
Pubmed
Yakel,
Single amino acid substitution affects desensitization of the 5-hydroxytryptamine type 3 receptor expressed in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Zhang,
Synaptic currents generated by neuronal acetylcholine receptors sensitive to alpha-bungarotoxin.
1996,
Pubmed
