Kainate receptors (KARs) are glutamate receptors with ionotropic and metabotropic activity composed of the GluK1-GluK5 subunits. We previously reported that KARs modulate excitatory and inhibitory transmission in the olfactory bulb (OB). Zinc, which is highly concentrated in the OB, also appears to modulate OB synaptic transmission via actions at other ionotropic glutamate receptors (i.e., AMPA, NMDA). However, few reports of effects of zinc on recombinant and/or native KARs exist and none have involved the OB. In the present study, we investigated the effects of exogenously applied zinc on OB KARs expressed by mitral/tufted (M/T) cells. We found that 100 µM zinc inhibits currents evoked by various combinations of KAR agonists (kainate or SYM 2081) and the AMPA receptor antagonist SYM 2206. The greatest degree of zinc-mediated inhibition was observed with coapplication of zinc with the GluK1- and GluK2-preferring agonist SYM 2081 plus SYM 2206. This finding is consistent with prior reports of zinc's inhibitory effects on some recombinant (homomeric GluK1 and GluK2 and heteromeric GluK2/GluK4 and GluK2/GluK5) KARs, although potentiation of other (GluK3, GluK2/3) KARs has also been described. It is also of potential importance given our previously reported molecular data suggesting that OB neurons express relatively high levels of GluK1 and GluK2. Our present findings suggest that a physiologically relevant concentration of zinc modulates KARs expressed by M/T cells. As M/T cells are targets of zinc-containing olfactory sensory neurons, synaptically released zinc may influence odor information-encoding synaptic circuits in the OB via actions at KARs.

中文翻译：

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锌调节嗅球海藻酸盐受体。

海藻酸酯受体（KARs）是具有离子和代谢活性的谷氨酸受体，由GluK1-GluK5亚基组成。我们先前曾报道，KARs调节嗅球（OB）中的兴奋性和抑制性传递。高度集中在OB中的锌似乎也通过对其他离子型谷氨酸受体（即AMPA，NMDA）的作用来调节OB突触传递。但是，关于锌对重组KAR和/或天然KAR的影响的报道很少，并且没有涉及OB的报道。在本研究中，我们调查了外源应用锌对二尖瓣/簇状（M / T）细胞表达的OB KAR的影响。我们发现100 µM的锌会抑制KAR激动剂（海藻酸盐或SYM 2081）和AMPA受体拮抗剂SYM 2206的各种组合引起的电流。锌与首选GluK1和GluK2激动剂SYM 2081加SYM 2206并用时，观察到最大程度的锌介导的抑制作用。这一发现与先前锌对某些重组体（同质GluK1和GluK2和异源异构体）的抑制作用相一致。 GluK2 / GluK4和GluK2 / GluK5）KAR，尽管也已经描述了其他（GluK3，GluK2 / 3）KAR的增强作用。考虑到我们先前报道的分子数据表明OB神经元表达相对较高水平的GluK1和GluK2，这也具有潜在的重要性。我们目前的发现表明，生理上相关的锌浓度可调节M / T细胞表达的KAR。由于M / T细胞是含锌嗅觉感觉神经元的靶标，