Smith D O, Lowe D, Temkin R, Jensen P, Hatt H
Department of Physiology, University of Wisconsin, Madison 53706, USA.
J Neurosci. 1995 May;15(5 Pt 2):3905-12. doi: 10.1523/JNEUROSCI.15-05-03905.1995.
In cultured embryonic chick motoneurons, glutamate-activated currents rise quickly and then decay rapidly to relatively small steady-state current levels. Dopaminergic modulation of these receptors was studied using patch-clamp recording techniques. At concentrations > or = 10 nM, dopamine enhanced glutamate-activated currents by about 200%. This enhancement was diminished by the nonspecific dopamine receptor antagonist S(+)-apomorphine and the more specific D1 receptor antagonist SCH23390, and it was mimicked by the D1 partial agonist SKF38393. Glutamate receptor desensitization rate was not altered in the presence of dopamine. Enhancement was specific to the kainate component. Current-variance analysis indicated that in the presence of dopamine the conductances of glutamate-activated channels were not altered but that the relative fraction of kainate-type channels activated by glutamate increased. Intracellular cAMP levels increased by 33% following exposure to 100 microM dopamine. The effects of elevated cAMP or protein kinase A (PKA) were tested by including 100 microM cAMP or PKA, respectively, in the recording pipette solution. This increased the kainate-activated currents specifically. Dopaminergic enhancement was not observed when a PKA inhibitor was in the pipette. mRNA encoding D1 was detected in the spinal cord by a reverse transcription, polymerase chain-reaction amplification procedure. Thus, dopamine is acting most probably on an avian homolog of the D1 receptor family. We conclude that dopamine causes cAMP to increase, which results in increased activation of kainate-gated channels during glutamate-mediated transmission.
在培养的胚胎鸡运动神经元中，谷氨酸激活的电流迅速上升，然后迅速衰减至相对较小的稳态电流水平。使用膜片钳记录技术研究了这些受体的多巴胺能调节作用。当多巴胺浓度≥10 nM时，可使谷氨酸激活的电流增强约200%。这种增强作用可被非特异性多巴胺受体拮抗剂S(+)-阿扑吗啡和更具特异性的D1受体拮抗剂SCH23390减弱，而D1部分激动剂SKF38393可模拟这种增强作用。在多巴胺存在的情况下，谷氨酸受体脱敏率未发生改变。增强作用对海人藻酸成分具有特异性。电流-方差分析表明，在多巴胺存在时，谷氨酸激活通道的电导未改变，但谷氨酸激活的海人藻酸型通道的相对比例增加。暴露于100 μM多巴胺后，细胞内cAMP水平升高了33%。分别在记录电极内液中加入100 μM cAMP或蛋白激酶A (PKA)，以测试cAMP或PKA升高的作用。这特异性地增加了海人藻酸激活的电流。当电极内液中存在PKA抑制剂时，未观察到多巴胺能增强作用。通过逆转录-聚合酶链反应扩增程序在脊髓中检测到了编码D1的mRNA。因此，多巴胺很可能作用于D1受体家族的禽类同源物。我们得出结论，多巴胺导致cAMP增加，从而在谷氨酸介导的传递过程中导致海人藻酸门控通道的激活增加。
