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Titolo:
Ca2+-sensitive inhibition by Pb2+ of alpha 7-containing nicotinic acetylcholine receptors in hippocampal neurons
Autore:
Mike, A; Pereira, EFR; Albuquerque, EX;
Indirizzi:
Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 t Therapeut, Baltimore, MD 21201 USA Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Ciencias Biomed, Dept Farmacol Bas & Clin, BR-21944 Rio De Janeiro, Brazil Univ Fed Rio de JaneiroRio De Janeiro Brazil BR-21944 e Janeiro, Brazil
Titolo Testata:
BRAIN RESEARCH
fascicolo: 1, volume: 873, anno: 2000,
pagine: 112 - 123
SICI:
0006-8993(20000804)873:1<112:CIBPOA>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTORS; LONG-TERM POTENTIATION; LEAD-EXPOSURE; CULTURED HIPPOCAMPAL; NEUROBLASTOMA-CELLS; SELECTIVE BLOCKADE; COGNITIVE FUNCTION; RAT HIPPOCAMPUS; INORGANIC LEAD; CURRENTS;
Keywords:
lead; nicotinic receptors; acetylcholine; choline; electrophysiology; hippocampus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Albuquerque, EX Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, 655 W Baltimore St, Baltimore, MD 21201 USA Univ Maryland 655 W Baltimore StBaltimore MD USA 21201 SA
Citazione:
A. Mike et al., "Ca2+-sensitive inhibition by Pb2+ of alpha 7-containing nicotinic acetylcholine receptors in hippocampal neurons", BRAIN RES, 873(1), 2000, pp. 112-123

Abstract

In the present study the patch-cramp technique was applied to cultured hippocampal neurons to determine the kinetics as well as the agonist concentration- and Ca2+-dependence of Pb2+-induced inhibition of alpha 7 nicotinic receptors (nAChRs). Evidence is provided that more than two-thirds of the inhibition by Pb2+ (3-30 mu M) of alpha 7 nAChR-mediated whole-cell currents (referred to as type IA currents) develops rapidly and is fully reversible upon washing. The estimated values for tau(onset) and tau(recovery) were 165 and 240 ms, respectively. The magnitude of the effect of Pb2+ was the same regardless of whether acetylcholine or choline was the agonist. Pre-exposure of the neurons for 800 ms to Pb2+ (30 mu M) decreased the amplitude andaccelerated the decay phase of currents evoked by moderate to high agonistconcentrations. In contrast, only the amplitude of currents evoked by low agonist concentrations was reduced when the neurons were exposed simultaneously to Pb2+ and the agonists. Taken together with the findings that Pb2+ reduces the frequency of opening and the mean open rime of alpha 7 nAChR channels, these data suggest that Pb2+ accelerates the rate of receptor desensitization. An additional reduction of type LA current amplitudes occurred after 2-min exposure of the neurons to Pb2+. This effect was not reversible upon washing of the neurons and was most Likely due to an intracellular action of Pb2+. Pb2+-induced inhibition of alpha 7 nAChRs, which was hindered by the enhancement of extracellular Ca2+ concentrations, may contribute to the neurotoxicity of the heavy metal. (C) 2000 Elsevier Science B.V. All rights reserved.

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Documento generato il 31/05/20 alle ore 11:25:59