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
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1Key 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)