Zinc Modulates Olfactory Bulb Kainate Receptors. (21st January 2020)

• Record Type: Journal Article
• Authors: Blakemore, Laura J.; Trombley, Paul Q.
• Is Part Of: Neuroscience. Volume 428(2020)
• Page Start: 252
• Page End: 268
• Publication Date: 2020-01-21
• Subjects: AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- AMPAR AMPA receptor -- ANOVA analysis of variance -- AP5 2-amino-5-phosphonopentanoic acid -- ATPA (RS)-2-Amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid -- CNS central nervous system -- DDI dendrodendritic inhibition -- DIV days in vitro -- DRG dorsal root ganglion -- EC50 half maximal effective concentration -- EGTA ethylene glycol-bis(β-aminoethyl ether)-N, N, N′, N′-tetraacetic acid -- EPSC excitatory postsynaptic current -- EPSP excitatory postsynaptic potential -- ET cells external tufted cells -- GABA gamma-aminobutyric acid -- GAD glutamic acid decarboxylase -- GL glomerular layer -- GYKI 52466 1-(4-Aminophenyl)-4-methyl-7, 8-methylenedioxy-5H-2, 3-benzodiazepine hydrochloride -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- IC50 half maximal inhibitory concentration -- ICC immunocytochemical -- IPSC inhibitory postsynaptic current -- IPSP inhibitory postsynaptic potential -- ISH in situ hybridization -- JG cells juxtaglomerular cells -- K2 D'Agostino-Pearson omnibus -- KAR kainate receptor -- KS Kolmogorov-Smirnov -- M/T cell mitral/tufted cell -- mEPSC miniature EPSC -- NMDA N-methyl-d-aspartate -- NMDAR NMDA receptor -- OB olfactory bulb -- ON olfactory nerve -- ONL olfactory nerve layer -- OSN olfactory sensory neuron -- PG cell periglomerular cell -- RT-PCR reverse transcription polymerase chain reaction -- SEM standard error of mean -- SS steady-state -- SW Shapiro-Wilk -- SYM 2081 (2S, 4R) 4-methylglutamic acid -- SYM 2206 4-(4-Aminophenyl)-1, 2-dihydro-1-methyl-2-propylcarbamoyl-6, 7-methylenedioxyphthalazine -- TTX tetrodotoxin -- VGLUT1 vesicular glutamate transporter 1 -- ZnCl2 zinc chloride -- ZP1 Zinpyr-1; glutamate receptors -- olfaction -- kainate -- SYM 2081 -- SYM 2206; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.11.041
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Prior results show that kainate receptors (KARs) modulate excitatory and inhibitory transmission in the olfactory bulb. A KAR agonist (kainate or SYM 2081) with or without an AMPA receptor antagonist (SYM 2206) evoked KAR-mediated currents. Zinc inhibited currents evoked by kainate plus SYM 2206, SYM 2081, or SYM 2081 plus SYM 2206 in the olfactory bulb. Coapplication of zinc with a GluK1- and GluK2-preferring agonist (SYM 2081) plus SYM 2206 caused the greatest inhibition. Zinc may influence odor-encoding synaptic currents by effects at KARs. 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.