Kainate (KA) receptors (KARs) are important modulators of synaptic transmission. We studied here the role of KARs on glutamatergic synaptic transmission in the CA2 region of the hippocampus where the actions of these receptors are unknown. We observed that KA depresses glutamatergic synaptic transmission at Schaffer collateral-CA2 synapses; an effect that was antagonized by NBQX (a KA/AMPA receptors antagonist) under condition where AMPA receptors were previously blocked. The study of paired-pulse facilitation ratio, miniature responses, and fluctuation analysis indicated a presynaptic locus of action for KAR. Additionally, we determined the action mechanism for this depression of glutamate release mediated by the activation of KARs. We found that inhibition of protein kinase A suppressed the effect of KAR activation on evoked excitatory post-synaptic current, an effect that was not suppressed by protein kinase C inhibitors. Furthermore, in the presence of Pertussis toxin, the depression of glutamate release mediated by KAR activation was not present, invoking the participation of a G_i/o protein in this modulation. Finally, the KAR-mediated depression of glutamate release was not suppressed by treatments that affect calcium entry trough voltage-dependent calcium channels or calcium release from intracellular stores. We conclude that KARs present at these synapses mediate a depression of glutamate release through a mechanism that involves the activation of G protein and protein kinase A.

中文翻译：

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海马CA2区谷氨酸能突触传递的海人酸受体调节

红藻氨酸 (KA) 受体 (KAR) 是突触传递的重要调节剂。我们在这里研究了 KAR 对海马 CA2 区域谷氨酸能突触传递的作用，这些受体的作用未知。我们观察到 KA 抑制了 Schaffer 侧支-CA2 突触的谷氨酸能突触传递；在先前阻断 AMPA 受体的条件下，NBQX（一种 KA/AMPA 受体拮抗剂）会拮抗这种作用。对成对脉冲易化率、微型反应和波动分析的研究表明 KAR 的突触前作用轨迹。此外，我们确定了这种由 KAR 激活介导的谷氨酸释放抑制的作用机制。我们发现抑制蛋白激酶 A 抑制了 KAR 激活对诱发的兴奋性突触后电流的影响，这种影响不受蛋白激酶 C 抑制剂的抑制。此外，在百日咳毒素存在的情况下，不存在由 KAR 激活介导的谷氨酸释放抑制，从而调用了 G此调制中的_i/o蛋白质。最后，KAR 介导的谷氨酸盐释放抑制不会被影响钙通过电压依赖性钙通道进入或从细胞内储存的钙释放的治疗所抑制。我们得出结论，存在于这些突触中的 KAR 通过涉及 G 蛋白和蛋白激酶 A 激活的机制介导谷氨酸释放的抑制。