低渗透压对大鼠三叉神经节神经元GABA激活电流的抑制作用  

Inhibition of GABA-activated Currents by Hyposmolality in Rat Trigeminal Ganglion Neurons

作　　者：衡璐[1] 李爱[1] 胡新武[1] 陈筱雨[1] 刘长金[1] 

机构地区：[1]华中科技大学同济医学院基础医学院生理学系,武汉430030

出　　处：《华中科技大学学报（医学版）》2008年第1期5-9,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的探讨低渗透压对大鼠三叉神经节神经元γ-氨基丁酸(GABA)激活电流(IGABA)的调制作用及胞内信号转导机制。方法全细胞膜片钳技术。结果实验中大部分受检细胞(89.2%)对外加GABA(10～1000μmol/L)敏感,可产生一具有明显浓度依赖性的内向电流,该电流可被GABAA受体特异性拮抗剂荷包牡丹碱阻断。预加低渗透压(567.3、670.5、773.6kPa)对IGABA产生抑制作用,该抑制作用呈可逆性和非电压依赖性。低渗透压+GABA的量效曲线较单独的IGABA量效曲线明显下移,而两者的阈值和最大反应浓度基本不变,分别为10μmol/L和1000μmol/L;两条曲线的EC50值非常接近,分别为29.41μmol/L和33.02μmol/L;预加低渗透压后最大反应浓度时,IGABA的幅值减少了(31.38±2.13)%。低渗透压对IGABA的抑制作用可被瞬时感受器电位辣椒素4亚型(TRPV4)受体非特异性阻断剂钌红部分阻断,可被TRPV4受体激动剂4α-PDD增强。细胞外灌流蛋白激酶C(PKC)的抑制剂BIM可部分逆转低渗透压对IGABA的抑制作用。结论低渗透压作用于TRPV4受体,部分通过激活PKC途径来减少GABAA受体介导的电流,这可能是低渗透压对IGABA的调节机制之一。Objective To investigate the modulatory effect of hyposmolality on GABA-activated currents（IGABA） in cultured rat trigeminal ganglion（TG） neurons. Methods Whole-cell patch clamp technique was used. Results The results were as follows ：①The majority of examined neurons（89.2% ） were sensitive to GABA（10-1 000 μmol/L）. GABA activated inward currents in a concentration-dependent manner, and IGABA were blocked by bicuculline, a selective antagonist of the GABAA receptor;②When hyposmolality（567.3, 670.5, 773.6 kPa） was pre-applied extracellularly, it reduced IGABA significantly, This inhibitory effect was reversible and voltage-independent. The concentration-response curve of GABA was shifted downward by hyposmolality without any change of the threshold value. The values of two curves were very close（33.02 μmol/L and 29.41 μmol/L respectively）. H yposmolality decreased the maximal amplitude of IGABA by（31.38 ± 2. 13）%. ③This inhibitory effect was reversed by ruthenium red, a nonselective TRPV4 receptor antagonist, and was increased by 4α-PDD, a selective TRPV4 receptor agonist;④Pre-application of BIM, a PKC inhibitor, partially reversed the inhibitory effect of hyposmolality. Conclusion Hyposmolality inhibited IGABA through activation of TRPV4 receptor. The inhibition was mediated partially through activation of PKC system, By inhibiting IGABA, TRPV4 suppressed the signal transmission at central end of primary sensory neuron via enhanced presynaptic inhibition. This is probably one of the mechanisms by which hyposmolality participates in peripheral antinociception.

关 键 词：低渗透压 GABAA受体 TRPV4受体 三叉神经节神经元 全细胞膜片钳 

分 类 号：R322.85[医药卫生—人体解剖和组织胚胎学]