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rdf:type |
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lifeskim:mentions |
umls-concept:C0013030,
umls-concept:C0030685,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0034826,
umls-concept:C0039067,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1314939,
umls-concept:C1416614,
umls-concept:C1444748,
umls-concept:C1514758,
umls-concept:C1711351,
umls-concept:C1963578
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pubmed:issue |
1
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pubmed:dateCreated |
2007-6-13
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pubmed:abstractText |
KCNQ2 and KCNQ3 subunits encode for the muscarinic-regulated current (I(KM)), a sub-threshold voltage-dependent K+ current regulating neuronal excitability. In this study, we have investigated the involvement of I(KM) in dopamine (DA) release from rat striatal synaptosomes evoked by elevated extracellular K+ concentrations ([K+]e) and by muscarinic receptor activation. [3H]dopamine ([3H]DA) release triggered by 9 mmol/L [K+]e was inhibited by the I(KM) activator retigabine (0.01-30 micromol/L; Emax = 54.80 +/- 3.85%; IC50 = 0.50 +/- 0.36 micromol/L). The I(KM) blockers tetraethylammonium (0.1-3 mmol/L) and XE-991 (0.1-30 micromol/L) enhanced K+-evoked [3H]DA release and prevented retigabine-induced inhibition of depolarization-evoked [3H]DA release. Retigabine-induced inhibition of K+-evoked [3H]DA release was also abolished by synaptosomal entrapment of blocking anti-KCNQ2 polyclonal antibodies, an effect prevented by antibody pre-absorption with the KCNQ2 immunizing peptide. Furthermore, the cholinergic agonist oxotremorine (OXO) (1-300 micromol/L) potentiated 9 mmol/L [K+]e-evoked [3H]DA release (Emax = 155 +/- 9.50%; EC50 = 25 +/- 1.80 micromol/L). OXO (100 micromol/L)-induced [3H]DA release enhancement was competitively inhibited by pirenzepine (1-10 nmol/L) and abolished by the M3-preferring antagonist 4-diphenylacetoxy N-methylpiperidine methiodide (1 micromol/L), but was unaffected by the M1-selective antagonist MT-7 (10-100 nmol/L) or by Pertussis toxin (1.5-3 microg/mL), which uncouples M2- and M4-mediated responses. Finally, OXO-induced potentiation of depolarization-induced [3H]DA release was not additive to that produced by XE-991 (10 micromol/L), was unaffected by retigabine (10 micromol/L), and was abolished by synaptosomal entrapment of anti-KCNQ2 antibodies. Collectively, these findings indicate that, in rat striatal nerve endings, I(KM) channels containing KCNQ2 subunits regulate depolarization-induced DA release and that I(KM) suppression is involved in the reinforcement of depolarization-induced DA release triggered by the activation of pre-synaptic muscarinic heteroreceptors.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carbamates,
http://linkedlifedata.com/resource/pubmed/chemical/D 23129,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ2 Potassium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ3 Potassium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/Kcnq2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Kcnq3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Muscarinic Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Muscarinic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylenediamines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Presynaptic
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-3042
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pubmed:author |
pubmed-author:AnnunziatoLucioL,
pubmed-author:BarreseVincenzoV,
pubmed-author:D'AmicoMoniaM,
pubmed-author:IannottiFabio ArturoFA,
pubmed-author:LavergataFrancescoF,
pubmed-author:MartireMariaM,
pubmed-author:MiceliFrancescoF,
pubmed-author:PanzaElisabettaE,
pubmed-author:PreziosiPaoloP,
pubmed-author:TaglialatelaMaurizioM,
pubmed-author:ViggianoDavideD
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pubmed:issnType |
Print
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
179-93
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pubmed:meshHeading |
pubmed-meshheading:17437547-Animals,
pubmed-meshheading:17437547-Blotting, Western,
pubmed-meshheading:17437547-CHO Cells,
pubmed-meshheading:17437547-Carbamates,
pubmed-meshheading:17437547-Cricetinae,
pubmed-meshheading:17437547-Cricetulus,
pubmed-meshheading:17437547-Dopamine,
pubmed-meshheading:17437547-Electrophysiology,
pubmed-meshheading:17437547-Fluorescent Antibody Technique,
pubmed-meshheading:17437547-KCNQ2 Potassium Channel,
pubmed-meshheading:17437547-KCNQ3 Potassium Channel,
pubmed-meshheading:17437547-Male,
pubmed-meshheading:17437547-Microscopy, Confocal,
pubmed-meshheading:17437547-Muscarinic Agonists,
pubmed-meshheading:17437547-Muscarinic Antagonists,
pubmed-meshheading:17437547-Neostriatum,
pubmed-meshheading:17437547-Nerve Endings,
pubmed-meshheading:17437547-Patch-Clamp Techniques,
pubmed-meshheading:17437547-Phenylenediamines,
pubmed-meshheading:17437547-Rats,
pubmed-meshheading:17437547-Rats, Wistar,
pubmed-meshheading:17437547-Receptors, Muscarinic,
pubmed-meshheading:17437547-Receptors, Presynaptic,
pubmed-meshheading:17437547-Synaptosomes
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pubmed:year |
2007
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pubmed:articleTitle |
Involvement of KCNQ2 subunits in [3H]dopamine release triggered by depolarization and pre-synaptic muscarinic receptor activation from rat striatal synaptosomes.
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pubmed:affiliation |
Institute of Pharmacology, School of Medicine, Catholic University of S. Heart, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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