酒精对大鼠颈上神经节P2X_4受体介导的ATP-激活电流的调制及机制  

Inhibition of Ethanol on ATP-activated current mediated by rat P2X_4 receptors

作　　者：彭芳[1] 齐小伟[1] 张玉芹[2] 

机构地区：[1]长江大学医学院机能学部,湖北荆州434023 [2]武汉科技大学医学院生理学教研室,湖北武汉430065

出　　处：《中国现代医学杂志》2015年第13期13-17,共5页China Journal of Modern Medicine

基　　金：湖北省教育厅重点科研项目(No:20081108)

摘　　要：目的研究酒精对大鼠颈上神经节P2X4受体介导的ATP-激活电流（IATP）的调制及机制。方法将大鼠颈上神经节P2X4受体表达在非洲爪蟾卵母细胞中,应用双电极电压钳技术记录P2X4受体介导的IATP及酒精对IATP的影响。结果 11-500 mmol/L的酒精浓度依赖性地抑制P2X4受体介导的IATP,这种抑制效应是可逆的,当细胞外的酒精被冲洗后,IATP可恢复到对照值;260 mmol/L的酒精使P2X4受体介导的IATP量-效曲线平行右移,最大电流（Emax）不变,半数有效浓度（EC50）增大,浓度大于500 mmol/L的酒精不能使EC50继续增大;3酒精对IATP的抑制不具有电压依赖性,且不改变翻转电位;41 mmol/L的镁离子和10 mmol/L的酒精分别能抑制10μmol/L ATP诱发的电流,当两者同时加入到细胞外液（两者的终浓度不改变）时,对IATP的抑制呈现叠加效应。结论 1酒精对表达在非洲爪蟾卵母细胞上大鼠颈上神经节P2X4受体介导的IATP具有抑制效应,这种抑制效应具有浓度依赖性、可逆性和无电压依赖性,可能是酒精通过对P2X4受体的变构调节实现的;2酒精和镁离子在P2X4受体胞外环上可能具有不同的调制位点。【Objective】To study the effects of ethanol on ATP-activated current（IATP） mediated by rat P2X4 receptors.【Methods】The rat P2X4 receptors were expressed in Xenopus oocytes by microinjection technique. The effects of ethanol on P2X4 receptors were recorded by two-electrode voltage clamp. 【Results】 ① Ethanol（1 -500mmol/L） inhibited IATPmediated by rat P2X4 receptors in a concentration-dependent manner. The current could recover after the extracellular ethanol was washed away. ② Ethanol（60 mmol/L） shifted the dose-response curve to right in a parallel manner, and increased the EC50from（15.9 ± 2.2） μmol/L to（24.6 ± 3.1） μmol/L. The Emax did not change. When the concentration of ethanol was greater than 500 mmol/L, the EC50 did not increase any more. ③Changing membrane potential from-80 m V to ＋20 m V had not significant effect on ethanol inhibition of IATP, and the reversal potential was not changed by applying ethanol. ④Mg^2＋（1 mmol/L） and ethanol（10 mmol/L） could inhibit IATPby（39.0 ± 3.8） % and（19.0 ± 1.6） % respectively, when co-applying them could produce a synergistic effect.【Conclusions】①Ethanol may inhibit IATPmediated by rat P2X4 receptors through allosteric regulation. ②Mg^2＋and ethanol might have different modulatory sites on the ectodomain of P2X4 receptors.

关 键 词：酒精 镁离子 P2X4受体 爪蟾卵母细胞 双电极电压钳技术 

分 类 号：R-332[医药卫生] R338