Electrophysiological study of endocannabinoid 2-AG protecting rat cau-dal nucleus neurons from injury via voltage-gated calcium channels
10.3969/j.issn.1000-4718.2025.07.002
- VernacularTitle:内源性大麻素2-AG通过电压门控钙通道拮抗大鼠尾核神经元损伤的电生理研究
- Author:
Shiyu ZHU
1
;
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;宜昌市三峡中心人民医院神经内科,湖北 宜昌 443002
- Publication Type:Journal Article
- Keywords:
2-arachidonoyl glycerol;
kainic acid;
voltage-gated calcium channels;
caudate nucleus;
cannabi-noid receptor 1
- From:
Chinese Journal of Pathophysiology
2025;41(7):1259-1266
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate the regulatory effect of the endocannabinoid 2-arachidonoyl glycerol(2-AG)on voltage-gated calcium channels(VGCCs)in caudate nucleus(CN)neurons subjected to kainic acid(KA)-induced damage,and to elucidate the underlying mechanisms involved.METHODS:Primary cultured CN neu-rons from neonatal Sprague-Dawley(SD)rats were treated with KA to establish an excitotoxic cellular model.The whole-cell patch-clamp technique was utilized to assess the effects of 2-AG on KA-induced excitotoxicity,along with the changes in the electrical properties of VGCCs.This included evaluations of current density,current-voltage relationships,and the kinetics of channel activation and inactivation.RESULTS:Treatment with KA significantly increased the current density and altered the electrical properties of VGCCs,as indicated by a reduction in the half-inactivation voltage and a shift of the inactivation curve towards depolarized potentials.Notably,KA did not affect the activation characteristics of VGCCs.Ad-ministration of exogenous 2-AG or the application of the monoacylglycerol lipase inhibitor URB602,which inhibits 2-AG degradation and elevates intracellular levels of 2-AG,effectively inhibited the KA-induced increase in VGCC current den-sity and the depolarization shift of the inactivation curve,highlighting the involvement of cannabinoid receptor 1(CB1R).CONCLUSION:The endocannabinoid 2-AG can modulate the function of VGCCs in CN neurons via the CB1R pathway,offering protective effects against excitotoxic damage induced by KA.
