Effect of 2-AG on A-type potassium channel currents in primarily cul-tured rat caudate nucleus neurons with kainic acid-induced injury
10.3969/j.issn.1000-4718.2023.12.001
- VernacularTitle: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
- Author:
Shiyu ZHU
1
,
2
;
Yongli LU
;
Zicheng LI
;
Hongwei YANG
Author Information
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
2. 宜昌市三峡中心人民医院神经内科,湖北 宜昌 443002
- Keywords:
2-arachidenoylglycerol;
kainic acid;
A-type potassium channels;
caudate nucleus;
cannabinoid receptor 1
- From:
Chinese Journal of Pathophysiology
2023;39(12):2113-2122
- CountryChina
- Language:Chinese
-
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.
