Surmeier D J, Eberwine J, Wilson C J, Cao Y, Stefani A, Kitai S T
Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163.
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10178-82. doi: 10.1073/pnas.89.21.10178.
Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1 dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+ current. The D2 agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+ currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in whole-cell recordings, whereas quinpirole consistently (6/10) enhanced currents--suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3 receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3 receptors.
黑质的多巴胺能神经元为新纹状体提供主要的神经调节输入之一。最近的原位杂交实验表明，突触后多巴胺受体在纹状体黑质和纹状体苍白球神经元中是分离的。我们通过检查选择性多巴胺能激动剂对钠电流的神经调节作用以及用多巴胺受体cDNA探测单细胞反义RNA群体，在急性分离的、逆行标记的纹状体黑质神经元中测试了这一假设。在大多数检测的神经元中（20/31），应用D1多巴胺受体激动剂SKF 38393可降低诱发的全细胞钠电流。D2激动剂喹吡罗和溴隐亭有混合效应；在大多数神经元中（23/42），全细胞钠电流降低，但在其他神经元中（8/42），电流增加。在细胞贴附式膜片钳记录中，浴加SKF 38393像在全细胞记录中一样降低电流，而喹吡罗则持续（6/10）增强电流——这表明D2样受体可能通过膜限定和非限定途径起作用。诱发电流的变化是由峰值电导的调节和稳态失活电压依赖性的适度改变引起的。多巴胺受体cDNA Southern印迹的反义RNA探针始终（5/5）显示单个纹状体黑质神经元中存在D1、D2和D3受体mRNA。这些发现表明，与严格的受体分离假设相反，许多纹状体黑质神经元共定位功能性D1、D2和D3受体。
