Dopamine D1-like receptor activation excites rat striatal large aspiny neurons in vitro
Dopamine D1-like receptor activation excites rat striatal large aspiny neurons in vitro
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DOI：
10.1523/jneurosci.18-14-05180.1998
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发表时间：
1998-07-15
影响因子：
5.3
通讯作者：
Kawaguchi, Y
中科院分区：
文献类型：
--
作者：
Aosaki, T;Kiuchi, K;Kawaguchi, Y
本研究的目的是从电生理角度阐明多巴胺和D-1样多巴胺受体激动剂SKF38393对纹状体大型刺激性神经元(胆碱能中间神经元)膜兴奋性的作用。用全细胞和穿孔膜片钳记录大鼠脑片上的纹状体胆碱能神经元。多巴胺浴(1-100微米)可引起去极化/内向电流，膜电导增加、降低或不变，呈剂量依赖关系。这种作用可被D-1样多巴胺受体拮抗剂SCH23390所拮抗。在23个细胞中测定的多巴胺诱导电流的电流-电压关系表明存在两种电导。在10个细胞中，电流在-94 mV处反转，大致等于K+平衡电位(E-K)；在3个细胞中，I-V曲线保持平行，而在10个细胞中，电流在-42 mV处反转，这表明参与了阳离子通透通道。在低Na+溶液中，外加K+浓度的变化使E-K的反转电位发生了变化。在2 mM Ba2+溶液中观察到的电流在-28 mV时反转。多巴胺的上述作用可被腺酰环化酶激活剂SKF38393(1~50 mU M)或Forsklin(10 MU M)模拟，并可被腺酰环化酶抑制剂SCH23390(10 MU M)或SQ22536(300 MU M)阻断。这些数据表明，首先，多巴胺通过D-1介导的抑制静息K+电导和开放非选择性阳离子通道来去极化纹状体大神经元，其次，这两种机制都是由腺苷环化酶依赖的途径介导的。
The aim of this study was to elucidate electrophysiologically the actions of dopamine and SKF38393, a D-1-like dopamine receptor agonist, on the membrane excitability of striatal large aspiny neurons (cholinergic interneurons). Whole-cell and perforated patch-clamp recordings were made of striatal cholinergic neurons in rat brain slice preparations. Bath application of dopa mine (1-100 mu M) evoked a depolarization/inward current with an increase, a decrease, or no change in membrane conductance in a dose-dependent manner. This effect was antagonized by SCH23390, a D-1-like dopamine receptor antagonist. The current-voltage relationships of the dopamine-induced current determined in 23 cells suggested two conductances. In 10 cells the current reversed at -94 mV, approximately equal to the K+ equilibrium potential (E-K); in three cells the I-V curves remained parallel, whereas in 10 cells the current reversed at -42 mV, which suggested an involvement of a cation permeable channel. Change in external K+ concentration shifted the reversal potential as expected for E-K in low Na+ solution. The current observed in 2 mM Ba2+ -containing solution reversed at -28 mV. These actions of dopamine were mimicked by application of SKF38393 (1-50 mu M) or forskolin (10 mu M), an adenylyl cyclase activator, and were blocked by SCH23390 (10 mu M) or SQ22536 (300 mu M), an inhibitor of adenylyl cyclase. These data indicate, first, that dopamine depolarizes the striatal large aspiny neurons by a D-1-mediated suppression of resting K+ conductance and an opening of a nonselective cation channel and, second, that both mechanisms are mediated by an adenylyl cyclase-dependent pathway.