SKF38393抑制大鼠DRG分离神经元GABA-激活电流

在大鼠新鲜分离ＤＲＧ神经元标本上应用全细胞膜片箝记录,观察了多巴胺Ｄ１受体的选择性激动剂ＳＫＦ３８３９３ＨＣＩ对ＧＡＢＡ－激活电流的作用。大部分受检细胞对ＧＡＢＡ敏感,１０＾－６－１０＾－３－ｍｏｌ／Ｌ ＧＡＢＡ可于引起呈剂量依赖性的明显去敏感作用的内向电流。

Inhibition by SKF38393 of GABA-activated currents in rat DRG neurons

Experiments were performed on neurons freshly isolated from rat DRG using whole-cell patch-clamp techniques. The majority of the neurons examined were sensitive to GABA (60/70) in the concentration range from 10(-6) to 10(-3) mol/L, showing obvious desensitization. In the 60 GABA-sensitive cells, responses induced by selective agonist of dopamine D1 receptor SKF38393 (+/-) SKF38393HCL] manifested three types: (1) outward current (7/60); (2) inward current (5/60) and (3) no detectable response (48/60). As compared with GABA-activated current, the amplitude of SKF38393-activated current are smaller and showed no apparent desensitization. When the neurons were treated with SKF38393 prior to application of GABA for 30 s, the GABA-activated current in majority of the cells (53/60) was inhibited, while the remaining six showed no effect. The effect of SKF38393 was dose dependent. That is, with SKF38393 at concentration of 10(-7), 10(-6), 10(-5) and 10(-4) mol/L, the GABA-activated current was inhibited by (24.8 +/- 2.6)% (n = 7), (26.8 +/- 1.5)% (n = 7), (35.6 +/- 1.2)% (n = 8) and (45.6 +/- 2.3)% (n = 8) respectively. By intracellular application of 10(-4) mol/L H-7, a potent inhibitor of protein kinase, the inhibitory effect of SKF38393 was abolished completely, a results suggesting that the inhibition by SKF38393 of the GABA-activated current might be a result of intracellular phosphorylation of GABAA receptor.