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

• 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

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.

采用膜片钳技术研究了多巴胺（DA）对纹状体胆碱能中间神经元GABA能突触传递的调节作用。多巴胺对纹状体胆碱能中间神经元GABA能抑制性突触后电流（IPSC）的抑制作用呈浓度依赖性。用DA受体激动剂或拮抗剂的药理学分析表明，D_2样受体参与。对微型IPSC的分析表明DA的作用位于突触前位点。此外，使用钙通道亚型特异性阻断剂的分析表明N型钙通道和突触前D_2样受体之间的选择性偶联（Momiyama &古贺，J.Physiol.523，479-492，2001）。这是第一个鉴定参与DA诱导的突触前调制突触传递的钙通道亚型的报道。最近的研究表明，N型通道的贡献仅限于几种中枢突触中出生后早期的年龄（Iwasaki et al.，神经科学杂志，2000）。因此，进一步的分析进行了纹状体GABA能突触，以阐明与DA诱导的抑制的变化相关的N型通道的贡献的发育变化。随着年龄的增长，N型通道的贡献逐渐减少，直到P60，但并没有完全消失。同时，D_2样受体介导的突触前抑制作用也降低，与N型通道的选择性偶联保持不变（Momiyama，J. Physiol.，546，483-490，2003）。这是第一个研究的发展变化的调制中枢突触传递G-蛋白偶联受体与变化的贡献，一定的钙通道亚型传输。

项目成果

Momiyama, T.: "Calcium channel subtypes mediating central synaptic transmis sion."Folia Pharmacologica Japonica. 119(4). 235-240 (2002)

Momiyama, T.：“介导中枢突触传递的钙通道亚型。”Folia Pharmacologica Japonica。

Kaifii, T. et al.: "Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice."Journal of Clinical Investigation. 111(3). 323-332 (2003)

Kaifii, T. 等人：“DAP12 缺陷小鼠的骨石症和丘脑髓鞘减少症伴突触变性。”临床研究杂志。

籾山俊彦: "中枢シナプス伝達とカルシウムチャネル"Clinical Neuroscience. 21(2). 226-227 (2003)

Toshihiko Momiyama：“中枢突触传递和钙通道”临床神经科学 21(2)。

Toshihiko Momiyama: "Parallel decrease in ω-conotoxin-sensitive transmission and dopamine induced inhibition at the striatal synapse of developing rats"Journal of Physiology. 546(2). 483-490 (2003)

Toshihiko Momiyama：“在发育中的大鼠的纹状体突触中，ω-芋螺毒素敏感性传递和多巴胺诱导的抑制同时减少”，生理学杂志 546(2) 483-490 (2003)。

Toshihiko Momiyama: "Catecholamine Research : From Molecular Insights to Clinical Medicine"Kluwer Academic/Plenum Publishers. 558 (2002)

Toshihiko Momiyama：“儿茶酚胺研究：从分子洞察到临床医学”Kluwer Academy/Plenum 出版社。