机构：[1]Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA[2]Department of Neurology, Xuanwu Hospital of Capital University of Medical Sciences, Beijing, China神经内科首都医科大学宣武医院[3]Division of Neurobiology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA[4]Departments of Neuroscience, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
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 (V (H) ) 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 mum), 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.
基金：
the Marjorie Newsome and Sandra Solheim Aiken Funds and the Women’s Board of the Barrow Neurological Institute.
第一作者机构：[1]Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA
通讯作者：
通讯机构：[1]Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA
推荐引用方式(GB/T 7714)：
Jie Wu,Piu Chan,Katherine M. Schroeder,et al.1-Methyl-4-phenylpridinium (MPP+)-induced functional run-down of GABA(A) receptor-mediated currents in acutely dissociated dopaminergic neurons[J].JOURNAL OF NEUROCHEMISTRY.2002,83(1):87-99.doi:10.1046/j.1471-4159.2002.01099.x.
APA：
Jie Wu,Piu Chan,Katherine M. Schroeder,Kevin Ellsworth&L. Donald L. Partridge.(2002).1-Methyl-4-phenylpridinium (MPP+)-induced functional run-down of GABA(A) receptor-mediated currents in acutely dissociated dopaminergic neurons.JOURNAL OF NEUROCHEMISTRY,83,(1)
MLA：
Jie Wu,et al."1-Methyl-4-phenylpridinium (MPP+)-induced functional run-down of GABA(A) receptor-mediated currents in acutely dissociated dopaminergic neurons".JOURNAL OF NEUROCHEMISTRY 83..1(2002):87-99
