Chen X, Kombian S B, Zidichouski J A, Pittman Q J
Neuroscience Research Group, University of Calgary, Alberta, Canada.
Neuroscience. 1999 May;90(2):457-68. doi: 10.1016/s0306-4522(98)00594-6.
Nystatin-perforated patch recordings were made from rat parabrachial neurons in an in vitro slice preparation to examine the effect of dopamine on parabrachial cells and on excitatory synaptic transmission in this nucleus. In current clamp mode, dopamine reduced the amplitude of the evoked excitatory postsynaptic potential without significant change in membrane potential. In cells voltage-clamped at -65 mV, dopamine dose dependently and reversibly decreased evoked, pharmacologically isolated, excitatory postsynaptic currents with an EC50 of 31 microM. The reduction in excitatory postsynaptic current was accompanied by an increase in paired pulse ratio (a protocol used to detect presynaptic site of action) with no change in the holding current or in the decay of the evoked excitatory postsynaptic currents. In addition, dopamine altered neither postsynaptic (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate-induced currents, nor steady-state current voltage curves. Miniature excitatory postsynaptic current analysis revealed that dopamine caused a rightward shift of the frequency-distribution curve with no change in the amplitude-distribution curve, which is consistent with a presynaptic mechanism. The dopamine-induced attenuation of the excitatory postsynaptic current was almost completely blocked by the D1-like receptor antagonist SCH23390 (10 microM), although the D2-like antagonist sulpiride (10 microM) also partially blocked it. Combined application of both antagonists blocked all dopamine-induced synaptic effects. The synaptic effect of dopamine was mimicked by the D1-like agonist SKF38393 (50 microM), but the D2-1ike agonist quinpirole (50 microM) also had a small effect. Combined application of both agonists did not produce potentiated responses. Dopamine's effect on the excitatory postsynaptic current was independent of serotonin, GABA and adenosine receptors, but may have some interactions with adrenergic receptors. These results suggest that dopamine directly modulates excitatory synaptic events in the parabrachial nucleus predominantly via presynaptic D1-like receptors.
在体外脑片制备中，采用制霉菌素穿孔膜片钳记录技术，从大鼠臂旁核神经元记录信号，以研究多巴胺对臂旁核细胞以及该核团兴奋性突触传递的影响。在电流钳模式下，多巴胺降低了诱发的兴奋性突触后电位的幅度，而膜电位无显著变化。在钳制电压为-65 mV的细胞中，多巴胺剂量依赖性且可逆地降低了诱发的、药理学分离的兴奋性突触后电流，其半数有效浓度（EC50）为31微摩尔。兴奋性突触后电流的降低伴随着配对脉冲比率的增加（一种用于检测突触前作用位点的实验方案），而钳制电流或诱发的兴奋性突触后电流的衰减没有变化。此外，多巴胺既不改变突触后（±）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸诱导的电流，也不改变稳态电流-电压曲线。微小兴奋性突触后电流分析显示，多巴胺使频率分布曲线向右移动，而幅度分布曲线无变化，这与突触前机制一致。多巴胺诱导的兴奋性突触后电流衰减几乎完全被D1样受体拮抗剂SCH23390（10微摩尔）阻断，尽管D2样拮抗剂舒必利（10微摩尔）也能部分阻断。两种拮抗剂联合应用可阻断所有多巴胺诱导的突触效应。多巴胺的突触效应可被D1样激动剂SKF38393（50微摩尔）模拟，但D2样激动剂喹吡罗（50微摩尔）也有较小作用。两种激动剂联合应用未产生增强反应。多巴胺对兴奋性突触后电流的作用独立于5-羟色胺、γ-氨基丁酸和腺苷受体，但可能与肾上腺素能受体有一些相互作用。这些结果表明，多巴胺主要通过突触前D1样受体直接调节臂旁核的兴奋性突触活动。
