可乐定对背根神经节神经元GABA激活电流的抑制作用

本实验在新鲜分离大鼠背根神经节（ＤＲＧ）细胞上应用全细胞膜片的箝记录研究贤上腺素α２－受体激动剂可乐定（ｃｌｏｎｉｄｉｎｅ）对ＧＡＢＡ－激活电流的调制作用。发现缘大多数ＤＲＧ细胞对ＧＡＢＡ（１０＾－６￣１０＾－３ｍｏｌ／Ｌ）敏感（７２／７５）,产生浓度依赖性的内向电流;并且可被ｂｉｃｕｃｕｌｉｎｅ（１０＾－５￣１０＾－４ｍｏｌ／Ｌ）所阻断。在多数细胞中（５１／７２）预加可乐定（１０＾－８￣１０＾－

Inhibitory effects of clonidine on GABA-activated currents in rat DRG neurons

Whole-cell patch-clamp recordings were performed on neurons from freshly isolated rat dorsal root ganglion (DRG) to investigate modulatory effects of clonidine, an alpha 2-adrenoceptor agonist, on GABA-activated currents. In the majority of the neurons examined (72/75), GABA (10(-6)-10(-3) mol/L) induced a concentration-dependent inward current, which could be blocked by bicuculine (10(-4)-10(-5) mol/L). In 51 out of 72 cells, pretreatment with different dosages of clonidine (10(-8)-10(-4) mol/L) decreased the GABA (10(-4) mol/L)-activated current by 8.5%, 19.0%, 33.4%, 44.4% and 40.3%, respectively, while clonidine itself only induced a slight inward current in a few cells (12/72). The inhibitory action of clonidine blockable by yohimbine (10(-4) mol/L) was voltage-independent and did not change the membrane conductance during the activation of GABAA receptor. Unlike NA, (-)-isoproternol (10(-4)-10(-5) mol/L) exerted no effect on GABA-activated currents. Intracellular application of H-7 (10(-4) mol/L) via micropipette resulted in a significant blockade of clonidine inhibition (19/20) except one cell showing only a slight inhibition (11.2%). The results suggest that the inhibitory effect of clonidine on GABA-activated currents in DRG neurons might involve phosphorylation of GABAA receptor following activation of alpha 2-adrenoceptor through a mechanism of intracellular transduction.