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内源性大麻素2-AG对海人藻酸诱导损伤的大鼠尾状核神经元A型钾通道电流的调制作用

朱时钰 陆永利 李自成 杨红卫

中国病理生理杂志2023,Vol.39Issue(12):2113-2122,10.
中国病理生理杂志2023,Vol.39Issue(12):2113-2122,10.DOI:10.3969/j.issn.1000-4718.2023.12.001

内源性大麻素2-AG对海人藻酸诱导损伤的大鼠尾状核神经元A型钾通道电流的调制作用

Effect of 2-AG on A-type potassium channel currents in primarily cul-tured rat caudate nucleus neurons with kainic acid-induced injury

朱时钰 1陆永利 2李自成 2杨红卫2

作者信息

  • 1. 三峡大学国家中医药管理局中药药理科研三级实验室,湖北 宜昌 443002||宜昌市三峡中心人民医院神经内科,湖北 宜昌 443002
  • 2. 三峡大学国家中医药管理局中药药理科研三级实验室,湖北 宜昌 443002||肿瘤微环境与免疫治疗湖北省重点实验室(三峡大学),湖北 宜昌 443002||三峡大学基础医学院机能学系,湖北 宜昌 443002
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摘要

Abstract

AIM:To explore the modulation of 2-arachidonoylglycerol(2-AG)on A-type potassium channels injured by kainic acid(KA)and its molecular mechanism.METHODS:Primary cultured caudate nucleus(CN)neurons were treated with KA to establish a neuroexcitatory toxicity model.Whole-cell patch clamp recording was performed to ob-serve the changes of electrical activity of A-type potassium channels induced by KA-induced excitatory toxicity and 2-AG-mediated neuroprotective effect.RESULTS:In cultured CN neurons,patch clamp experiments confirmed that KA signifi-cantly decreased the A-type potassium channel current(IA)density and changed the electrical function of CN neurons:the slope(k)of inactivation curve and the recovery time constant(τ)after inactivation of A-type potassium channels in CN neurons were significantly increased.The experiments showed that the increase in 2-AG level,whether using 2-AG direct-ly or application of monoacylglycerol lipase inhibitor URB602 to decrease 2-AG metabolism and increase 2-AG level indi-rectly,inhibited the KA-induced reduction of IA density and the changes of electrical activity of A-type potassium channels through cannabinoid receptor 1(CB1R):2-AG effectively antagonized the KA-induced increases in τ value and k value for inactivation of A-type potassium channels,which accelerated the recovery process after inactivation of the channels.CONCLUSION:The changes of the electrical characteristics of A-type potassium channels may be one of the mecha-nisms of KA-induced excitotoxic injury of CN neurons.The 2-AG plays a neuroprotective role in KA-induced neuroexcit-atory toxic model by regulating the function of A-type potassium channels through CB1R.

关键词

2-花生四烯酰甘油/海人藻酸/A型钾通道/尾状核/大麻素受体1

Key words

2-arachidenoylglycerol/kainic acid/A-type potassium channels/caudate nucleus/cannabinoid receptor 1

分类

医药卫生

引用本文复制引用

朱时钰,陆永利,李自成,杨红卫..内源性大麻素2-AG对海人藻酸诱导损伤的大鼠尾状核神经元A型钾通道电流的调制作用[J].中国病理生理杂志,2023,39(12):2113-2122,10.

基金项目

国家自然科学基金面上项目(No.30970930) (No.30970930)

中国病理生理杂志

OA北大核心CSCDCSTPCD

1000-4718

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