Metabotropic Actions of Kainate Receptors in the Control of Glutamate Release in the Hippocampus
Metabotropic Actions of Kainate Receptors in the Control of Glutamate Release in the Hippocampus
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DOI：
10.1007/978-1-4419-9557-5_4
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发表时间：
2011-01-01
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影响因子：
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通讯作者：
Sihra, Talvinder S.
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作者：
Rodriguez-Moreno, Antonio;Sihra, Talvinder S.
红藻氨酸盐型谷氨酸受体（KAR）在结构上呈现其他离子型谷氨酸受体（iGluR）家族成员（NMDA和AMPA受体）的凭证，但在功能上通常声称是代谢型操作模式的实例。在本章中，我们描述了这些代谢型作用的KARs在海马CA 3谢弗侧支（SC）-CA 1锥体细胞（PC）突触和齿状回颗粒细胞苔藓纤维（MF）-CA 3 PC突触谷氨酸释放的调制。作为SC末端上的自身受体，KAR通过依赖于百日咳毒素敏感性G（i/o）蛋白的机制抑制SC-CA 1 PC突触处谷氨酸的释放，该机制被认为通过其G β γ亚基与Ca 2+通道功能的降低偶联。在MF-CA 3 PC突触，MF终端上的自身受体响应直径取决于激动剂浓度。在低KA浓度（100 nM）时，涉及百日咳毒素敏感性G（i/o）蛋白的机制被调用，以抑制AC活性，从而抑制PKA活性。考虑到GABA释放的异突触调节KARs与代谢型的工作方式，因此有令人信服的证据表明，这些离子型谷氨酸受体参与谷氨酸释放的非经典调制，不依赖于其典型的离子型活性。
Kainate-type glutamate rcceptors (KARs) structurally present the credentials of the other ionotropic glutamate receptor (iGluR) family members (NMDA and AMPA receptors), but functionally often purport examples of a metabotropic mode of operation. In the present chapter, we describe these metabotropic roles of KARs in the modulation of glutamate release in the hippocampus at CA3 Schaffer Collateral (SC)-CA1 Pyramidal Cell (PC) synapses and dentate gyrus granule cell Mossy Fiber (MF)-CA3 PC synapses. As autoreceptors on SC terminals, KARs inhibit the release of glutamate at SC-CA1 PC synapses through a mechanism dependent on a pertussis toxin-sensitive G(i/o) protein thought to couple via its G beta gamma subunit to a decrease in Ca2+ channel function. At MF-CA3 PC synapses, autoreceptors on MF terminals respond diametrically depending on the agonist concentration. At low KA concentrations (100 nM), a mechanism involving a pertussis toxin-sensitive G(i/o) protein is invoked to inhibit AC activity and thereby suppress PKA activity. Taken together with the heterosynaptic regulation of GABA release by KARs working with a metabotropic modus operandi, there is therefore compelling evidence that these ionotropic glutamate receptors are involved in a noncanonical modulation of glutamate release that does not rely on their typical ionotropic activity.