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急性分离的大鼠齿状颗粒细胞中γ-氨基丁酸A受体的药理学特性

Pharmacological properties of gamma-aminobutyric acidA receptors from acutely dissociated rat dentate granule cells.

作者信息

Kapur J, Macdonald R L

机构信息

Department of Neurology, University of Michigan Medical Center, Ann Arbor 48104-1687, USA.

出版信息

Mol Pharmacol. 1996 Sep;50(3):458-66.

PMID:8794882
Abstract

The pharmacological properties of gamma-aminobutyric acid (GABA) type A receptor (GABAR) currents recorded from hippocampal dentate granule cells acutely dissociated from 28-35-day-old rats were characterized using the whole-cell patch-clamp technique. Granule cells were voltage-clamped to 0 mV, and GABA was applied using a modified U-tube rapid-application technique. All granule cells were moderately sensitive to GABA (EC50 = 47 microM). All granule cell GABAR currents were uniformly sensitive to Zn2+ (IC50 = 29 microM), diazepam (EC50 = 158 nM), zolpidem (EC50 = 75 nM), and dimethoxyl-4-ethyl-beta-carboline-3-carboxylate (IC50 = 60 nM). GABAR currents from only 50% of granule cells were sensitive to loreclezole (EC50 = 9 microM). These data suggest that hippocampal dentate granule cells expressed GABARs with distinctive pharmacological properties of two types: loreclezole-sensitive and -insensitive receptors. It is likely that these distinctive properties were due to the specific GABAR subtypes that assembled to produce distinct granule cell GABAR isoforms.

摘要

采用全细胞膜片钳技术,对从28至35日龄大鼠急性分离的海马齿状颗粒细胞中记录到的γ-氨基丁酸(GABA)A型受体(GABAR)电流的药理学特性进行了表征。将颗粒细胞电压钳制在0 mV,使用改良的U型管快速施加技术施加GABA。所有颗粒细胞对GABA均呈中度敏感(半数有效浓度[EC50]=47μM)。所有颗粒细胞的GABAR电流对锌离子(半数抑制浓度[IC50]=29μM)、地西泮(EC50=158 nM)、唑吡坦(EC50=75 nM)和二甲氧基-4-乙基-β-咔啉-3-羧酸酯(IC50=60 nM)均表现出一致的敏感性。仅50%的颗粒细胞的GABAR电流对氯雷唑(EC50=9μM)敏感。这些数据表明,海马齿状颗粒细胞表达了具有两种不同药理学特性的GABAR:对氯雷唑敏感和不敏感的受体。这些独特的特性可能归因于组装产生不同颗粒细胞GABAR亚型的特定GABAR亚型。

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