Dopaminergic modulation of NMDA-induced whole cell currents in neostriatal neurons in slices: Contribution of calcium conductances
Dopaminergic modulation of NMDA-induced whole cell currents in neostriatal neurons in slices: Contribution of calcium conductances
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DOI：
10.1152/jn.1998.79.1.82
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发表时间：
1998-01-01
影响因子：
2.5
通讯作者：
Levine, MS
中科院分区：
文献类型：
--
作者：
Cepeda, C;Colwell, CS;Levine, MS
本实验旨在检查切片中可视化新纹状体神经元中 N-甲基-D-天冬氨酸 (NMDA) 受体激活介导的多巴胺 (DA) 对全细胞电流的调节。首先，我们评估了 DA、D-1 和 D-2 受体激动剂调节 NMDA 受体激活诱导的膜电流的能力。这些实验的结果表明，DA 增强了中型新纹状体神经元中 NMDA 诱导的电流。 NMDA 电流的增强发生在三种不同的保持电位下，尽管在 -30 mV 时更明显。它由 D-1 受体介导，因为它被 D-1 激动剂模拟，并通过暴露于 D-2 拮抗剂而被阻断。 D-2 受体的激活对 NMDA 诱导的膜电流产生不一致的影响。对 NMDA 电流的影响要么减少、增加，要么没有影响。其次，vie 检查了固有的电压依赖性电导对 NMDA 电流的 DA 增强的贡献。 K+电导的阻断并不能阻止NMDA电流的DA增强。然而，电压激活的 Ca2+ 电导对 DA 调节做出了主要贡献。二氢吡啶 L 型 Ca2+ 通道阻滞剂硝苯地平和甲氧基维拉帕米 (D-600) 显着降低但并未完全消除 DA 调节 NMDA 电流的能力。 D-1 受体激动剂 SKF 38393 还增强了新纹状体神经元中的 Ba2+ 电流。总之，这些发现为 DA、NMDA 受体激活和二氢吡啶敏感 Ca2+ 电导之间复杂的相互作用提供了证据，以控制新纹状体中等大小神经元的反应性。
The present experiments were designed to examine dopamine (DA) modulation of whole cell currents mediated by activation of N-methyl-D-aspartate (NMDA) receptors in visualized neostriatal neurons in slices. First, we assessed the ability of DA, D-1 and D-2 receptor agonists to modulate membrane currents induced by activation of NMDA receptors. The results of these experiments demonstrated that DA potentiated NMDA-induced currents in medium-sized neostriatal neurons. Potentiation of NMDA currents occurred at three different holding potentials, although it was more pronounced at -30 mV. It was mediated by D-1 receptors, because it was mimicked by D-1 agonists and blocked by exposure to a D-2 antagonist. Activation of D-2 receptors produced inconsistent effects on NMDA-induced membrane currents. Either decreases, increases, or no effects on NMDA currents occurred. Second, vie examined the contributions of intrinsic, voltage-dependent conductances to DA potentiation of NMDA currents. Blockade of K+ conductances did not prevent DA enhancement of NMDA currents. However, voltage-activated Ca2+ conductances provided a major contribution to DA modulation. The dihydropyridine L-type Ca2+ channel blockers, nifedipine, and methoxyverapamil (D-600), markedly reduced but did not totally eliminate the ability of DA to modulate NMDA currents. The D-1 receptor agonist SKF 38393 also enhanced Ba2+ currents in neostriatal neurons. Together, these findings provide evidence for a complex interplay between DA, NMDA receptor activation and dihydropyridine-sensitive Ca2+ conductances in controlling responsiveness of neostriatal medium-sized neurons.