可乐定对背根神经节神经元GABA激活电流的抑制作用
王钦文, 李琴, 李之望
同济医科大学实验医学研究中心;武汉市儿童医院
摘要
本实验在新鲜分离大鼠背根神经节(DRG)细胞上应用全细胞膜片箝记录研究肾上腺素α2-受体激动剂可乐定(clonidine)对CABA-激活电流的调制作用。发现绝大多数DRG细胞对GABA(10-6~10-3mol/L)敏感(72/75),产生浓度依赖性的内向电流;并且可被bicuculine(10-5~10-4mol/L)所阻断。在多数细胞中(51/72)预加可乐定(10-8~10-4mol/L)后,GABA-激活电流受到明显抑制,抑制率分别为8.5%,19.0%,33.4%,44.4%和40.3%;此作用可被育亨宾(10-4mol/L)所阻断。可乐定本身只在少数细胞(12/72)膜上引起很小的内向流。不同于NA的是,β-受体激动剂异丙肾上腺素(10-5~10-4mol/L)对GABA激活电流无影响(n=9)。胞内预加H-7(10-4mol/L),大多数细胞(19/20)中可乐定的抑制作用均明显地被阻断,只有一例细胞尚有轻微的抑制作用(11.2%)。本文结果提示:可乐定对GABA激活电流的抑制可能是由于α2-受体激活后,通过胞内转导,而引起GABAA受体蛋白磷酸化的结果。
关键词: 背根神经节; 肾上腺素α2-受体; 可乐定; γ-氨基丁酸; 全细胞膜片箝记录; 抑制作用
Li Wenjue
Department of Physiology, Shanghai College of Traditional Chinese Medicine. Shanghai, China
Abstract
Whole-cell patch-clamp recordings were performed on neurons from freshly isolated rat dorsal root ganglion (DRG) to investigate modulatory effects of clonidine,an α2 adrenoceptor agonist,on GABA-activated currents.In the majority of the neurons examined(72/75),GABA(10-6~10-3 mol/L)induced a concentration-dependent inward current,Which could be blocked by bicuculine(10-4~10-5 mol/L).In 51 out of 72 cells,pretreatment with different dosages of clonidine(10-8~10-4 mol/L)decreased the GABA(10-4 mol/L)-activated current by 8.5%,19.0%,33.4%,44.4% and 40.3%,respectively,while clonidine itself only induced a slight inward current in a few cells (12/72).The inhibitory action of clonidine blockable by yohimbine (10-4 mol/L)was voltage-independent and did not change the membrane conductance during the activation of GABAA receptor.Unlike NA,(-)-isoproternol(10-4~10-5 mol/L)exerted no effect on GABA-activated currents.
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引用本文:
王钦文, 李琴, 李之望. 可乐定对背根神经节神经元GABA激活电流的抑制作用[J]. 生理学报 1998; 50 (1): .
Li Wenjue. . Acta Physiol Sin 1998; 50 (1): (in Chinese with English abstract).