Negrete-Díaz José V, Sihra Talvinder S, Delgado-García José M, Rodríguez-Moreno Antonio
División de Neurociencias, Universidad Pablo de Olavide, Seville, Spain.
J Neurophysiol. 2006 Oct;96(4):1829-37. doi: 10.1152/jn.00280.2006. Epub 2006 Jun 28.
The mechanisms involved in the inhibition of glutamate release mediated by the activation of presynaptic kainate receptors (KARs) at the hippocampal mossy fiber-CA3 synapse are not well understood. We have observed a long-lasting inhibition of CA3 evoked excitatory postsynaptic currents (eEPSCs) after a brief application of kainate (KA) at concentrations ranging from 0.3 to 10 muM. The inhibition outlasted the change in holding current caused by the activation of ionotropic KARs in CA3 pyramidal cells, indicating that this action is not contingent on the opening of the receptor channels. The inhibition of the eEPSCs by KA was prevented by G protein and protein kinase A (PKA) inhibitors and was enhanced after stimulation of the adenylyl cyclase (AC) with forskolin. We conclude that KARs present at mossy fiber terminals mediate the inhibition of glutamate release through a metabotropic mechanism that involves the activation of an AC-second messenger cAMP-PKA signaling cascade.
海马苔藓纤维 - CA3突触处，由突触前红藻氨酸受体（KARs）激活介导的谷氨酸释放抑制机制尚未完全明确。我们观察到，在0.3至10 μM浓度范围内短暂应用红藻氨酸（KA）后，CA3诱发的兴奋性突触后电流（eEPSCs）出现持久抑制。这种抑制作用持续时间超过了CA3锥体细胞中离子型KARs激活所引起的钳制电流变化，表明该作用并非取决于受体通道的开放。KA对eEPSCs的抑制作用可被G蛋白和蛋白激酶A（PKA）抑制剂阻断，而在用福斯高林刺激腺苷酸环化酶（AC）后，抑制作用增强。我们得出结论，苔藓纤维终末处的KARs通过一种代谢型机制介导谷氨酸释放的抑制，该机制涉及AC - 第二信使环磷酸腺苷 - PKA信号级联反应的激活。
