Svoboda K R, Lupica C R
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
J Neurosci. 1998 Sep 15;18(18):7084-98. doi: 10.1523/JNEUROSCI.18-18-07084.1998.
The actions of mu- and delta-opioid agonists (DAMGO and DPDPE, respectively) on GABAergic interneurons in stratum oriens of area CA1 of the hippocampus were examined by using whole-cell voltage-clamp recordings in brain slices. Both agonists consistently generated outward currents of similar magnitude (15-20 pA) in the majority of cells. However, under control conditions, current-voltage (I/V) relationships revealed that only a small number of these cells (3 of 77) demonstrated clear increases in membrane conductance, associated with the activation of the potassium current known as Girk. These interneurons also exhibited a slowly activating, inwardly rectifying current known as Ih on hyperpolarizing step commands. Ih was blocked by the extracellular application of cesium (3-9 mM) or ZD 7288 (10-100 microM) but was insensitive to barium (1-2 mM). In an effort to determine whether the holding current changes were attributable to the modulation of Girk and/or Ih, we used known blockers of these ion channels (barium or cesium and ZD 7288, respectively). Extracellular application of cesium (3-9 mM) or ZD 7288 (25-100 microM) blocked Ih and significantly reduced the opioid-induced outward currents by 58%. Under these conditions the opioid agonists activated a potassium current with characteristics similar to Girk. Similarly, during barium (1-2 mM) application the opioid-induced outward currents were reduced by 46%, and a clear reduction in Ih and the whole-cell conductance was revealed. These data suggest that the opioids can modulate both Ih and Girk in the same population of stratum oriens interneurons and that the modulation of these ion channels can contribute to the inhibition of interneuron activity in the hippocampus.
通过在脑片上使用全细胞膜片钳记录技术，研究了μ-阿片受体激动剂（分别为DAMGO）和δ-阿片受体激动剂（分别为DPDPE）对海马CA1区海马下托层GABA能中间神经元的作用。在大多数细胞中，两种激动剂均持续产生幅度相似（15 - 20 pA）的外向电流。然而，在对照条件下，电流-电压（I/V）关系显示，这些细胞中只有少数（77个中的3个）表现出膜电导的明显增加，这与被称为Girk的钾电流的激活有关。这些中间神经元在超极化阶跃指令下还表现出一种缓慢激活的内向整流电流，称为Ih。Ih可被细胞外施加铯（3 - 9 mM）或ZD 7288（10 - 100 μM）阻断，但对钡（1 - 2 mM）不敏感。为了确定钳制电流的变化是否归因于Girk和/或Ih的调节，我们使用了这些离子通道的已知阻滞剂（分别为钡或铯以及ZD 7288）。细胞外施加铯（3 - 9 mM）或ZD 7288（25 - 100 μM）阻断了Ih，并使阿片类药物诱导的外向电流显著降低了58%。在这些条件下，阿片受体激动剂激活了一种具有与Girk相似特性的钾电流。同样，在施加钡（1 - 2 mM）期间，阿片类药物诱导的外向电流降低了46%，并且Ih和全细胞膜电导明显降低。这些数据表明，阿片类药物可以在同一群海马下托层中间神经元中调节Ih和Girk，并且这些离子通道的调节可能有助于抑制海马中间神经元的活动。
