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1-Methyl-4-phenylpridinium (MPP+)-induced functional run-down of GABA(A) receptor-mediated currents in acutely dissociated dopaminergic neurons.
Wu, Jie; Chan, Piu; Schroeder, Katherine M; Ellsworth, Kevin; Partridge, L Donald L.
Afiliação
  • Wu J; Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. jwu2@chw.ed
J Neurochem ; 83(1): 87-99, 2002 Oct.
Article em En | MEDLINE | ID: mdl-12358732
ABSTRACT
We have evaluated GABA(A)receptor function during treatment of 1-methyl-4-phenylpridinium (MPP+) using patch-clamp perforated whole-cell recording techniques in acutely dissociated dopaminergic (DAergic) neurons from rat substantia nigra compacta (SNc). Gamma-aminobutyric acid (GABA), glutamate or glycine induced inward currents (I(GABA), I(Glu), I(Gly)) at a holding potential (VH) of -45 mV. The I(GABA) was reversibly blocked by the GABA(A) receptor antagonist, bicuculline, suggesting that I(GABA) is mediated through the activation of GABA(A) receptors. During extracellular perfusion of MPP+ (1-10 microm), I(GABA) , but neither I(Glu) nor I(Gly), declined (termed run-down) with repetitive agonist applications, indicating that the MPP+-induced I(GABA) run-down occurred earlier than I(Gly) or I(Glu) under our experimental conditions. The MPP+-induced I(GABA) run-down can be prevented by a DA transporter inhibitor, mazindol, and can be mimicked by a metabolic inhibitor, rotenone. Using conventional whole-cell recording with different concentrations of ATP in the pipette solution, I(GABA) run-down can be induced by decreasing intracellular ATP concentrations, or prevented by supplying intracellular ATP, indicating that I(GABA) run-down is dependent on intracellular ATP concentrations. A GABA(A) receptor positive modulator, pentobarbital (PB), potentiated the declined I(GABA) and eliminated I(GABA) run-down. Corresponding to these patch-clamp data, tyrosine hydroxylase (TH) immunohistochemical staining showed that TH-positive cell loss was protected by PB during MPP+ perfusion. It is concluded that extracellular perfusion of MPP+ induces a functional run-down of GABA(A) receptors, which may cause an imbalance of excitation and inhibition of DAergic neurons.
Assuntos
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Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Dopamina / 1-Metil-4-fenilpiridínio / Receptores de GABA-A / Proteínas do Tecido Nervoso / Neurônios Idioma: En Ano de publicação: 2002 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Dopamina / 1-Metil-4-fenilpiridínio / Receptores de GABA-A / Proteínas do Tecido Nervoso / Neurônios Idioma: En Ano de publicação: 2002 Tipo de documento: Article