1‐Methyl‐4‐phenylpridinium (MPP+)‐induced functional run‐down of GABAA receptor‐mediated currents in acutely dissociated dopaminergic neurons
1‐Methyl‐4‐phenylpridinium (MPP+)‐induced functional run‐down of GABAA receptor‐mediated currents in acutely dissociated dopaminergic neurons
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1-甲基-4-苯基吡啶鎓 (MPP+) 诱导急性分离多巴胺能神经元中 GABAA 受体介导的电流功能下降
DOI：
10.1046/j.1471-4159.2002.01099.x
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发表时间：
2002
影响因子：
4.7
通讯作者：
L. Donald L. Partridge
中科院分区：
文献类型：
--
作者：
Jie Wu;P. Chan;K. M. Schroeder;Kevin Ellsworth;L. Donald L. Partridge
我们使用膜片钳穿孔全细胞记录技术在大鼠黑质（SNc）急性分离的多巴胺能（DA能）神经元中评价了1-甲基-4-苯基吡啶（MPP+）处理期间GABAA受体功能。γ-氨基丁酸（GABA）、谷氨酸或甘氨酸在保持电位（VH）为−45 mV时诱导内向电流（IGABA、IGlu、IGly）。 GABAA受体拮抗剂荷包牡丹碱可逆地阻断了IGABA，表明IGABA是通过激活GABAA受体介导的。在MPP+（1-10 μm）的细胞外灌注期间，IGABA（但不是IGlu或IGly）随着重复激动剂应用而下降（称为运行下降），表明在我们的实验条件下，MPP+诱导的IGABA运行下降发生早于IGly或IGlu。 MPP+诱导的IGABA下降可以通过DA转运蛋白抑制剂马吲哚来预防，并且可以通过代谢抑制剂鱼藤酮来模拟。使用移液管溶液中不同浓度ATP的常规全细胞记录，可通过降低细胞内ATP浓度诱导或通过供应细胞内ATP防止IGABA下降，表明IGABA下降依赖于细胞内ATP浓度。GABAA受体阳性调节剂戊巴比妥（PB）可增强下降的IGABA并消除IGABA下降。与这些膜片钳数据相对应，酪氨酸羟化酶（TH）免疫组织化学染色显示，在MPP+灌注期间，PB可保护TH阳性细胞丢失。得出结论，MPP+的细胞外灌注诱导GABAA受体的功能下降，这可能导致DA能神经元的兴奋和抑制失衡。
We have evaluated GABAA 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). γ‐Aminobutyric acid (GABA), glutamate or glycine induced inward currents (IGABA, IGlu, IGly) at a holding potential (VH) of −45 mV. The IGABA was reversibly blocked by the GABAA receptor antagonist, bicuculline, suggesting that IGABA is mediated through the activation of GABAA receptors. During extracellular perfusion of MPP+ (1–10 μm), IGABA, but neither IGlu nor IGly, declined (termed run‐down) with repetitive agonist applications, indicating that the MPP+‐induced IGABA run‐down occurred earlier than IGly or IGlu under our experimental conditions. The MPP+‐induced IGABA 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, IGABA run‐down can be induced by decreasing intracellular ATP concentrations, or prevented by supplying intracellular ATP, indicating that IGABA run‐down is dependent on intracellular ATP concentrations. A GABAA receptor positive modulator, pentobarbital (PB), potentiated the declined IGABA and eliminated IGABA 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 GABAA receptors, which may cause an imbalance of excitation and inhibition of DAergic neurons.
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DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
全细胞记录过程中γ-氨基丁酸A受体功能的“衰退”：磷酸化的可能作用。
影响因子：
3.6
作者：
Gyenes,M;Farrant,M;Farb,DH
通讯作者：
Farb,DH
DOI：
--
发表时间：
1992-04
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
D. Monte;E. Wu;L. Delanney;I. Irwin;J. Langston
通讯作者：
D. Monte;E. Wu;L. Delanney;I. Irwin;J. Langston
中枢神经元树突截除后微型抑制性突触后电流的 Ca(2) 依赖性可塑性。
DOI：
10.1152/jn.1995.73.5.1763
发表时间：
1995
期刊：
Journal of neurophysiology.
影响因子：
--
作者：
Soltesz,I;Mody,I
通讯作者：
Mody,I
DOI：
10.1016/0006-291x(85)91071-x
发表时间：
1985-01-01
影响因子：
3.1
作者：
CHIBA, K;TREVOR, AJ;CASTAGNOLI, N
通讯作者：
CASTAGNOLI, N