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多巴胺激活两种不同的受体,从而在一个已确定的突触处产生信号变化。

Dopamine activates two different receptors to produce variability in sign at an identified synapse.

作者信息

Magoski N S, Bulloch A G

机构信息

Department of Physiology and Biophysics, Neuroscience Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

出版信息

J Neurophysiol. 1999 Mar;81(3):1330-40. doi: 10.1152/jn.1999.81.3.1330.

DOI:10.1152/jn.1999.81.3.1330
PMID:10085359
Abstract

Chemical synaptic transmission was investigated at a central synapse between identified neurons in the freshwater snail, Lymnaea stagnalis. The presynaptic neuron was the dopaminergic cell, Right Pedal Dorsal one (RPeD1). The postsynaptic neuron was Visceral Dorsal four (VD4). These neurons are components of the respiratory central pattern generator. The synapse from RPeD1 to VD4 showed variability of sign, i.e., it was either inhibitory (monophasic and hyperpolarizing), biphasic (depolarizing followed by hyperpolarizing phases), or undetectable. Both the inhibitory and biphasic synapse were eliminated by low Ca2+/high Mg2+ saline and maintained in high Ca2+/high Mg2+ saline, indicating that these two types of connections were chemical and monosynaptic. The latency of the inhibitory postsynaptic potential (IPSP) in high Ca2+/high Mg2+ saline was approximately 43 ms, whereas the biphasic postsynaptic potential (BPSP) had approximately 12-ms latency in either normal or high Ca2+/high Mg2+ saline. For a given preparation, when dopamine was pressured applied to the soma of VD4, it always elicited the same response as the synaptic input from RPeD1. Thus, for a VD4 neuron receiving an IPSP from RPeD1, pressure application of dopamine to the soma of VD4 produced an inhibitory response similar to the IPSP. The reversal potentials of the IPSP and the inhibitory dopamine response were both approximately -90 mV. For a VD4 neuron with a biphasic input from RPeD1, pressure-applied dopamine produced a biphasic response similar to the BPSP. The reversal potentials of the depolarizing phase of the BPSP and the biphasic dopamine response were both approximately -44 mV, whereas the reversal potentials for the hyperpolarizing phases were both approximately -90 mV. The hyperpolarizing but not the depolarizing phase of the BPSP and the biphasic dopamine response was blocked by the D-2 dopaminergic antagonist (+/-) sulpiride. Previously, our laboratory demonstrated that both IPSP and the inhibitory dopamine response are blocked by (+/-) sulpiride. Conversely, the depolarizing phase of both the BPSP and the biphasic dopamine response was blocked by the Cl- channel antagonist picrotoxin. Finally, both phases of the BPSP and the biphasic dopamine response were desensitized by continuous bath application of dopamine. These results indicate that the biphasic RPeD1 --> VD4 synapse is dopaminergic. Collectively, these data suggest that the variability in sign (inhibitory vs. biphasic) at the RPeD1 --> VD4 synapse is due to activation of two different dopamine receptors on the postsynaptic neuron VD4. This demonstrates that two populations of receptors can produce two different forms of transmission, i.e., the inhibitory and biphasic forms of the single RPeD1 --> VD4 synapse.

摘要

在淡水蜗牛椎实螺(Lymnaea stagnalis)中,对已鉴定神经元之间的中枢突触处的化学突触传递进行了研究。突触前神经元是多巴胺能细胞,右足背侧神经元1(RPeD1)。突触后神经元是内脏背侧神经元4(VD4)。这些神经元是呼吸中枢模式发生器的组成部分。从RPeD1到VD4的突触表现出信号的变异性,即它要么是抑制性的(单相且超极化)、双相的(去极化后接着超极化阶段),要么无法检测到。抑制性和双相突触都被低钙/高镁盐溶液消除,并在高钙/高镁盐溶液中得以维持,这表明这两种连接类型是化学性的且为单突触。在高钙/高镁盐溶液中,抑制性突触后电位(IPSP)的潜伏期约为43毫秒,而双相突触后电位(BPSP)在正常或高钙/高镁盐溶液中的潜伏期约为12毫秒。对于给定的标本,当多巴胺被压力施加到VD4的胞体时,它总是引发与来自RPeD1的突触输入相同的反应。因此,对于从RPeD1接收IPSP的VD4神经元,向VD4胞体压力施加多巴胺会产生与IPSP相似的抑制性反应。IPSP和抑制性多巴胺反应的反转电位均约为 -90 mV。对于具有来自RPeD1双相输入的VD4神经元,压力施加多巴胺会产生与BPSP相似的双相反应。BPSP去极化阶段和双相多巴胺反应的反转电位均约为 -44 mV,而超极化阶段的反转电位均约为 -90 mV。BPSP和双相多巴胺反应的超极化而非去极化阶段被D - 2多巴胺能拮抗剂(±)舒必利阻断。此前,我们实验室已证明IPSP和抑制性多巴胺反应均被(±)舒必利阻断。相反,BPSP和双相多巴胺反应的去极化阶段被氯离子通道拮抗剂印防己毒素阻断。最后,通过持续浴加多巴胺,BPSP和双相多巴胺反应的两个阶段均出现脱敏。这些结果表明,双相的RPeD1 --> VD4突触是多巴胺能的。总体而言,这些数据表明RPeD1 --> VD4突触处信号(抑制性与双相性)的变异性是由于突触后神经元VD4上两种不同多巴胺受体的激活。这证明了两类受体可产生两种不同形式的传递,即单个RPeD1 --> VD4突触的抑制性和双相性形式。

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