Analysis of dynamics of D2-like receptors and calcium channels in striatal synaptic terminals

纹状体突触末梢 D2 样受体和钙通道的动态分析

基本信息

批准号：
13680904
负责人：
MOMIYAMA Toshihiko
金额：
$ 2.3万
依托单位：
Okazaki National Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680904/
关键词：
striatum acetylcholine dopamine D2-like receptors N-type calcium channels GABAergic IPSCs developmental change slice ラット GABA シナプス前D2タイプ受容体生後発達変化

项目摘要

A patch-clamp analysis was carried out using brain slices obtained from rats of 12-20 postnatal (P12-20) to elucidate the modulatory roles of dopamine (DA) in GABAergic synaptic transmission onto striatal cholinergic interneurons. Bath application of DA inhibited the GABAergic inhibitory postsynaptic currents (IPSCs) recorded in striatal cholinergic interneurons in a concentration-dependent manner. Pharmacological analysis using DA receptor agonists or antagonists suggests the involvement of D_2-like receptors. Analysis of miniature IPSCs suggests a presynaptic locus of DA's action. Furthermore, analysis using calcium channel subtype-specific blockers suggest the selective coupling between N-type calcium channels and presynaptic D_2-like receptors (Momiyama & Koga, J. Physiol. 523, 479-492, 2001). This is the first report that has identified the calcium channel subtype involved in DA-induced presynaptic modulation synaptic transmission.A recent study has demonstrated that the contribution of N-type channels is limited only to early postnatal age in several central synapses (Iwasaki et al., J. Neurosci., 2000). Therefore, further analysis was performed in this striatal GABAergic synapse to elucidate the developmental change in the contribution of N-type channels in association with the change in DA-induced inhibition. The contribution of N-type channels gradually decreased with age until P60, but did not absolutely disappear. In parallel, D_2-like receptor-mediated presynaptic inhibitory effect also decreased, with the selective coupling to N-type channels remain unchanged (Momiyama, J. Physiol., 546, 483-490, 2003). This is the first study of developmental change in the modulation of central synaptic transmission by G-protein-coupled receptors in association with a change in the contribution a certain calcium channel subtype to transmission.

使用从12-20个大鼠（P12-20）大鼠获得的脑切片进行了斑块夹分析，以阐明多巴胺（DA）在GABA能突触传播到纹状体胆碱能中间神经元中的调节作用。 DA的浴施用抑制了纹状体胆碱能中间神经元以浓度依赖性方式记录的GABA能抑制性突触后电流（IPSC）。使用DA受体激动剂或拮抗剂的药理学分析表明，D_2样受体的参与。微型IPSC的分析表明DA动作的突触前基因座。此外，使用钙通道亚型特异性阻滞剂进行分析表明，N型钙通道和突触前D_2样受体之间的选择性耦合（Momiyama＆Koga，J。Physiol。523，479-492，2001）。这是第一项报告，已经确定了参与DA诱导的突触前调节突触传播所涉及的钙通道亚型。一项最近的研究表明，N型通道的贡献仅限于几个中央突触中早期的早期年龄（IWASAKI等人，J.Neursci。，2000年）。因此，在该纹状体GABA能突触中进行了进一步的分析，以阐明N型通道与DA诱导的抑制作用变化有关的贡献的发育变化。 N型通道的贡献随着年龄的增长而逐渐减少，直到P60，但并非绝对消失。同时，D_2样受体介导的突触前抑制作用也降低了，选择性耦合到N型通道保持不变（Momiyama，J。Physiol。，546，483-490，2003）。这是对G蛋白偶联受体调节中央突触传播的发育变化的首次研究，以及贡献变化某些钙通道亚型对传播的贡献。