Zinc Modulates Olfactory Bulb Kainate Receptors

Abstract

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.

Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

“…Similarly, exogenous application of Zn 21 can inhibit kainate receptors in the olfactory bulb (Blakemore and Trombley, 2020). Similar to NMDA receptors, there is a relationship between Zn 21 inhibition and extracellular protons, wherein Zn 21 inhibition is reduced in acidic pH, the opposite of NMDA receptors (Mott et al, 2008).…”

Identifying candidate genes underlying isolated congenital anosmia

“…The gene with the highest priority score, SRE-K1IP1, encodes a protein involved in zinc ion binding activity. Zinc has been shown to modulate olfactory signaling at the level of both the olfactory sensory neuron 39 and the olfactory bulb, 40 and there is clinical evidence that intranasal administration of zinc can cause anosmia. 41 Here, we identified a highly deleterious frameshift mutation in SREK1IP1 within one family and seven additional individuals with ICA, suggesting that the role of this gene in olfactory signaling should be a top priority.…”

Evidence of new coronavirus infection in the upper respiratory tract

“…В этой ситуации рекомендованы контроль обонятельной функции в динамике и обонятельный тренинг. В какойто степени обосновано назначение масляных капель с витамином А и препаратов цинка [41][42][43].…”