摘要
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（60／70）对GABA敏感，10－6－10－3mol／LGABA可引起呈剂量依赖性的明显去敏感作用的内向电流。在这60个细胞中，预加SKF38393可引起三类膜反应如：（1）外向电流（7／60）；（2）内向电流（5／60）和（3）无反应（48／60）。与GANA激活的内向电流相比，SKF38393激活电流幅值较小，无明显去敏感现象。预加SKF3839330s对GABA-激活电流幅值的影响如下：产生抑制作用的为53／60，增强的为1／60，无明显作用的为6／60。在浓度10-7至10－4mol／L范围SKF38393对10－4mol／L的GANA-激活电流的抑制作用依赖于SKF38393的浓度。通过应用二次膜片箝（repatch）技术在同一细胞（n＝2）以及不同细胞组间（n＝14）进行对比，结果表明：细胞内加蛋白激酶抑制剂H－7后，SKF38393对GANA的抑制作用完全消除，看来SKF38393对GABA-激活电流的抑制作用可能是由于SKF38393使CABA受体通道复合体胞内磷酸化所致。
Experiments were Performed on neurons freshly isolated from rat DRG using wholecell 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 desensihzation. In the 60 GABA-sensitive cells, responses induced by selective agonist Of dopamine D1 receptor Sin8393 [ (±) 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 SKF38393activated 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 Sin8393 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 intracellulax 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 GABAactivated current might be a result of intracellular phosphorylation of GABAA receptor.
出处
《生理学报》
CAS
CSCD
北大核心
1998年第3期280-288,共9页
Acta Physiologica Sinica
基金
国家自然科学基金!39370239
关键词
背根神经节
SKF38393
Γ-氨基丁酸
GABA
电活动
dorsal root ganalion
whole-cell patch-clamp recoiling
dopahane D_1 receptor agonist SKF3839
GABA
inhibition
