{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T19:33:10Z","timestamp":1776022390343,"version":"3.50.1"},"reference-count":72,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T00:00:00Z","timestamp":1543449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"vor","delay-in-days":249,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS30888"],"award-info":[{"award-number":["NS30888"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:p>Kainate receptors are ligand-gated ion channels that have two major roles in the central nervous system: they mediate a postsynaptic component of excitatory neurotransmission at some glutamatergic synapses and modulate transmitter release at both excitatory and inhibitory synapses. Accumulating evidence implicates kainate receptors in a variety of neuropathologies, including epilepsy, psychiatric disorders, developmental delay, and cognitive impairment. Here, to gain a deeper understanding of the conformational changes associated with agonist binding and channel opening, we generate a series of Cys substitutions in the GluK2 kainate receptor subunit, focusing on the M3 helices that line the ion pore and form the bundle-crossing gate at the extracellular mouth of the channel. Exposure to 50 \u00b5M Cd produces direct activation of homomeric mutant channels bearing Cys substitutions in (A657C), or adjacent to (L659C), the conserved SYTANLAAF motif. Activation by Cd is occluded by modification with 2-aminoethyl MTS (MTSEA), indicating that Cd binds directly and specifically to the substituted cysteines. Cd potency for the A657C mutation (EC50 = 10 \u00b5M) suggests that binding involves at least two coordinating residues, whereas weaker Cd potency for L659C (EC50 = 2 mM) implies that activation does not require tight coordination by multiple side chains for this substitution. Experiments with heteromeric and chimeric channels indicate that activation by Cd requires Cys substitution at only two of the four subunits within a tetrameric receptor and that activation is similar for substitution within subunits in either the A\/C or B\/D conformations. We develop simple kinetic models for the A657C substitution that reproduce several features of Cd activation as well as the low-affinity inhibition observed at higher Cd concentrations (5\u201320 mM). Together, these results demonstrate rapid and reversible channel activation, independent of agonist site occupancy, upon Cd binding to Cys side chains at two specific locations along the GluK2 inner helix.<\/jats:p>","DOI":"10.1085\/jgp.201812234","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T14:34:21Z","timestamp":1543502061000},"page":"435-451","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Cadmium opens GluK2 kainate receptors with cysteine substitutions at the M3 helix bundle crossing"],"prefix":"10.1085","volume":"151","author":[{"given":"Timothy J.","family":"Wilding","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University Medical School, St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0400-3802","authenticated-orcid":true,"given":"James E.","family":"Huettner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University Medical School, St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2018,11,29]]},"reference":[{"key":"2023072705471686100_bib1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-1-4939-2845-3_3","article-title":"Cysteine modification: Probing channel structure, function and conformational change","volume":"869","author":"Akabas","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023072705471686100_bib2","doi-asserted-by":"publisher","first-page":"2617","DOI":"10.1523\/JNEUROSCI.2667-15.2016","article-title":"A molecular determinant of subtype-specific desensitization in ionotropic glutamate receptors","volume":"36","author":"Alsaloum","year":"2016","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1523\/JNEUROSCI.10-01-00011.1990","article-title":"ATP-activated channels in rat and bullfrog sensory neurons: Current-voltage relation and single-channel behavior","volume":"10","author":"Bean","year":"1990","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib4","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/S0896-6273(00)80710-2","article-title":"NMDAR channel segments forming the extracellular vestibule inferred from the accessibility of substituted cysteines","volume":"22","author":"Beck","year":"1999","journal-title":"Neuron."},{"key":"2023072705471686100_bib5","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1124\/mol.112.081398","article-title":"Kainate receptor signaling in pain pathways","volume":"83","author":"Bhangoo","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"2023072705471686100_bib6","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1523\/JNEUROSCI.3485-07.2008","article-title":"The activation gate and gating mechanism of the NMDA receptor","volume":"28","author":"Chang","year":"2008","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib7","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1016\/j.cell.2017.07.045","article-title":"Activation and desensitization mechanism of AMPA receptor-TARP complex by Cryo-EM","volume":"170","author":"Chen","year":"2017","journal-title":"Cell."},{"key":"2023072705471686100_bib8","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1212\/WNL.0000000000001524","article-title":"GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia","volume":"84","author":"Coutelier","year":"2015","journal-title":"Neurology."},{"key":"2023072705471686100_bib9","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.coph.2014.11.012","article-title":"Physiopathology of kainate receptors in epilepsy","volume":"20","author":"Cr\u00e9pel","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"2023072705471686100_bib10","doi-asserted-by":"publisher","first-page":"8281","DOI":"10.1523\/JNEUROSCI.19-19-08281.1999","article-title":"Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7","volume":"19","author":"Cui","year":"1999","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1126\/science.280.5360.69","article-title":"The structure of the potassium channel: Molecular basis of K+ conduction and selectivity","volume":"280","author":"Doyle","year":"1998","journal-title":"Science."},{"key":"2023072705471686100_bib12","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-60327-058-8_8","article-title":"Protein structure modeling with MODELLER","volume":"426","author":"Eswar","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"2023072705471686100_bib13","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1002\/mds.27315","article-title":"A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder","volume":"33","author":"Fern\u00e1ndez-Marmiesse","year":"2018","journal-title":"Mov. Disord."},{"key":"2023072705471686100_bib14","doi-asserted-by":"publisher","first-page":"15044","DOI":"10.1074\/jbc.M600442200","article-title":"A C-terminal lysine that controls human P2X4 receptor desensitization","volume":"281","author":"Fountain","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2023072705471686100_bib15","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/brain\/awx358","article-title":"De novo mutations in GRIN1 cause extensive bilateral polymicrogyria","volume":"141","author":"Fry","year":"2018","journal-title":"Brain."},{"key":"2023072705471686100_bib16","doi-asserted-by":"publisher","first-page":"35638","DOI":"10.1074\/jbc.M807226200","article-title":"An intersubunit hydrogen bond in the nicotinic acetylcholine receptor that contributes to channel gating","volume":"283","author":"Gleitsman","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2023072705471686100_bib17","doi-asserted-by":"publisher","first-page":"e129","DOI":"10.1212\/NXG.0000000000000129","article-title":"A gain-of-function mutation in the GRIK2 gene causes neurodevelopmental deficits","volume":"3","author":"Guzm\u00e1n","year":"2017","journal-title":"Neurol. Genet."},{"key":"2023072705471686100_bib18","volume-title":"Ion Channels of Excitable Membranes.","author":"Hille","year":"2001","edition":"Third edition"},{"key":"2023072705471686100_bib19","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1021\/cr9500390","article-title":"Structural and functional aspects of metal sites in biology","volume":"96","author":"Holm","year":"1996","journal-title":"Chem. Rev."},{"key":"2023072705471686100_bib20","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/S0896-6273(00)80571-1","article-title":"The activation gate of a voltage-gated K+ channel can be trapped in the open state by an intersubunit metal bridge","volume":"21","author":"Holmgren","year":"1998","journal-title":"Neuron."},{"key":"2023072705471686100_bib21","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1152\/jn.1996.76.1.510","article-title":"Homomeric and heteromeric ion channels formed from the kainate-type subunits GluR6 and KA2 have very small, but different, unitary conductances","volume":"76","author":"Howe","year":"1996","journal-title":"J. Neurophysiol."},{"key":"2023072705471686100_bib22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1113\/jphysiol.2014.272724","article-title":"Glutamate receptor pores","volume":"593","author":"Huettner","year":"2015","journal-title":"J. Physiol."},{"key":"2023072705471686100_bib23","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/S0028-3908(98)00082-3","article-title":"Antagonism of neuronal kainate receptors by lanthanum and gadolinium","volume":"37","author":"Huettner","year":"1998","journal-title":"Neuropharmacology."},{"key":"2023072705471686100_bib24","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/S0028-3908(97)00066-X","article-title":"Desensitization of kainate receptors by kainate, glutamate and diastereomers of 4-methylglutamate","volume":"36","author":"Jones","year":"1997","journal-title":"Neuropharmacology."},{"key":"2023072705471686100_bib25","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1523\/JNEUROSCI.22-06-02044.2002","article-title":"The NMDA receptor M3 segment is a conserved transduction element coupling ligand binding to channel opening","volume":"22","author":"Jones","year":"2002","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib26","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1126\/science.1251915","article-title":"Crystal structure of a heterotetrameric NMDA receptor ion channel","volume":"344","author":"Karakas","year":"2014","journal-title":"Science."},{"key":"2023072705471686100_bib27","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nature01280","article-title":"Coupling of agonist binding to channel gating in the GABA(A) receptor","volume":"421","author":"Kash","year":"2003","journal-title":"Nature."},{"key":"2023072705471686100_bib28","doi-asserted-by":"publisher","first-page":"4941","DOI":"10.1523\/JNEUROSCI.0660-04.2004","article-title":"Effects of the lurcher mutation on GluR1 desensitization and activation kinetics","volume":"24","author":"Klein","year":"2004","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib29","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/73877","article-title":"Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties","volume":"3","author":"Kohda","year":"2000","journal-title":"Nat. Neurosci."},{"key":"2023072705471686100_bib30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3389\/fnmol.2018.00113","article-title":"The LILI motif of M3-S2 linkers is a component of the NMDA receptor channel gate","volume":"11","author":"Ladislav","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"2023072705471686100_bib31","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/nature13548","article-title":"NMDA receptor structures reveal subunit arrangement and pore architecture","volume":"511","author":"Lee","year":"2014","journal-title":"Nature."},{"key":"2023072705471686100_bib32","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.neuron.2013.09.045","article-title":"Kainate receptors in health and disease","volume":"80","author":"Lerma","year":"2013","journal-title":"Neuron."},{"key":"2023072705471686100_bib33","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.ajhg.2016.07.013","article-title":"GRIN2D recurrent de novo dominant mutation causes a severe epileptic encephalopathy treatable with NMDA receptor channel blockers","volume":"99","author":"Li","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"2023072705471686100_bib34","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jneumeth.2006.05.027","article-title":"Empirical considerations regarding the use of ensemble-variance analysis of macroscopic currents","volume":"158","author":"Lingle","year":"2006","journal-title":"J. Neurosci. Methods."},{"key":"2023072705471686100_bib35","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0896-6273(00)80357-8","article-title":"Gated access to the pore of a voltage-dependent K+ channel","volume":"19","author":"Liu","year":"1997","journal-title":"Neuron."},{"key":"2023072705471686100_bib36","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1085\/jgp.201311000","article-title":"Q\/R site interactions with the M3 helix in GluK2 kainate receptor channels revealed by thermodynamic mutant cycles","volume":"142","author":"Lopez","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"2023072705471686100_bib37","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1523\/JNEUROSCI.4573-04.2005","article-title":"Glutamate receptor trafficking: Endoplasmic reticulum quality control involves ligand binding and receptor function","volume":"25","author":"Mah","year":"2005","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib38","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1016\/j.bpj.2017.07.028","article-title":"The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures","volume":"113","author":"Mayer","year":"2017","journal-title":"Biophys. J."},{"key":"2023072705471686100_bib39","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/nature19352","article-title":"Structural basis of kainate subtype glutamate receptor desensitization","volume":"537","author":"Meyerson","year":"2016","journal-title":"Nature."},{"key":"2023072705471686100_bib40","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1523\/JNEUROSCI.3567-07.2008","article-title":"pH-dependent inhibition of kainate receptors by zinc","volume":"28","author":"Mott","year":"2008","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib41","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1085\/jgp.201210786","article-title":"Probing the activation sequence of NMDA receptors with lurcher mutations","volume":"140","author":"Murthy","year":"2012","journal-title":"J. Gen. Physiol."},{"key":"2023072705471686100_bib42","doi-asserted-by":"publisher","first-page":"e34711","DOI":"10.7554\/eLife.34711","article-title":"An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups","volume":"7","author":"Perszyk","year":"2018","journal-title":"eLife."},{"key":"2023072705471686100_bib43","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1016\/j.bpj.2011.03.063","article-title":"Labeling of specific cysteines in proteins using reversible metal protection","volume":"100","author":"Puljung","year":"2011","journal-title":"Biophys. J."},{"key":"2023072705471686100_bib44","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.celrep.2012.01.003","article-title":"Assembly stoichiometry of the GluK2\/GluK5 kainate receptor complex","volume":"1","author":"Reiner","year":"2012","journal-title":"Cell Reports."},{"key":"2023072705471686100_bib45","doi-asserted-by":"publisher","first-page":"e35134","DOI":"10.1371\/journal.pone.0035134","article-title":"An alternating GluN1-2-1-2 subunit arrangement in mature NMDA receptors","volume":"7","author":"Riou","year":"2012","journal-title":"PLoS One."},{"key":"2023072705471686100_bib46","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0162-0134(98)10042-9","article-title":"Coordination geometries of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metalloproteins","volume":"71","author":"Rul\u00ed\u0161ek","year":"1998","journal-title":"J. Inorg. Biochem."},{"key":"2023072705471686100_bib47","doi-asserted-by":"publisher","first-page":"11295","DOI":"10.1523\/JNEUROSCI.5612-10.2011","article-title":"Arrangement of subunits in functional NMDA receptors","volume":"31","author":"Salussolia","year":"2011","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib48","doi-asserted-by":"publisher","first-page":"12230","DOI":"10.1523\/JNEUROSCI.3175-07.2007","article-title":"A domain linking the AMPA receptor agonist binding site to the ion pore controls gating and causes lurcher properties when mutated","volume":"27","author":"Schmid","year":"2007","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib49","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1046\/j.0953-816x.2001.01705.x","article-title":"Dominance of the lurcher mutation in heteromeric kainate and AMPA receptor channels","volume":"14","author":"Schwarz","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"2023072705471686100_bib50","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1113\/jphysiol.1980.sp013426","article-title":"The variance of sodium current fluctuations at the node of Ranvier","volume":"307","author":"Sigworth","year":"1980","journal-title":"J. Physiol."},{"key":"2023072705471686100_bib51","doi-asserted-by":"publisher","first-page":"3304","DOI":"10.1016\/S0006-3495(02)75331-9","article-title":"Staggering of subunits in NMDAR channels","volume":"83","author":"Sobolevsky","year":"2002","journal-title":"Biophys. J."},{"key":"2023072705471686100_bib52","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/S0896-6273(04)00008-X","article-title":"The outer pore of the glutamate receptor channel has 2-fold rotational symmetry","volume":"41","author":"Sobolevsky","year":"2004","journal-title":"Neuron."},{"key":"2023072705471686100_bib53","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1085\/jgp.200609718","article-title":"Subunit-specific contribution of pore-forming domains to NMDA receptor channel structure and gating","volume":"129","author":"Sobolevsky","year":"2007","journal-title":"J. Gen. Physiol."},{"key":"2023072705471686100_bib54","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/nature08624","article-title":"X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor","volume":"462","author":"Sobolevsky","year":"2009","journal-title":"Nature."},{"key":"2023072705471686100_bib55","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/S0026-895X(25)09275-2","article-title":"Competitive antagonism of glutamate receptor channels by substituted benzazepines in cultured cortical neurons","volume":"41","author":"Swartz","year":"1992","journal-title":"Mol. Pharmacol."},{"key":"2023072705471686100_bib56","doi-asserted-by":"publisher","first-page":"8475","DOI":"10.1074\/jbc.275.12.8475","article-title":"The Lurcher mutation of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit enhances potency of glutamate and converts an antagonist to an agonist","volume":"275","author":"Taverna","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2023072705471686100_bib57","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1124\/pr.109.002451","article-title":"Glutamate receptor ion channels: Structure, regulation, and function","volume":"62","author":"Traynelis","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"2023072705471686100_bib58","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1021\/acs.biochem.7b00891","article-title":"Structural mechanisms of gating in ionotropic glutamate receptors","volume":"57","author":"Twomey","year":"2018","journal-title":"Biochemistry."},{"key":"2023072705471686100_bib59","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/nature23479","article-title":"Channel opening and gating mechanism in AMPA-subtype glutamate receptors","volume":"549","author":"Twomey","year":"2017","journal-title":"Nature."},{"key":"2023072705471686100_bib60","doi-asserted-by":"publisher","first-page":"13604","DOI":"10.1073\/pnas.0801854105","article-title":"A conserved salt bridge critical for GABA(A) receptor function and loop C dynamics","volume":"105","author":"Venkatachalan","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072705471686100_bib61","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.neuron.2012.08.027","article-title":"Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand binding domain dimer interface","volume":"76","author":"Veran","year":"2012","journal-title":"Neuron."},{"key":"2023072705471686100_bib62","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.neuropharm.2017.04.041","article-title":"A novel NMDA receptor positive allosteric modulator that acts via the transmembrane domain","volume":"121","author":"Wang","year":"2017","journal-title":"Neuropharmacology."},{"key":"2023072705471686100_bib63","doi-asserted-by":"publisher","first-page":"9470","DOI":"10.1523\/JNEUROSCI.2826-05.2005","article-title":"Q\/R site editing controls kainate receptor inhibition by membrane fatty acids","volume":"25","author":"Wilding","year":"2005","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib64","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1085\/jgp.200810009","article-title":"Amino acid substitutions in the pore helix of GluR6 control inhibition by membrane fatty acids","volume":"132","author":"Wilding","year":"2008","journal-title":"J. Gen. Physiol."},{"key":"2023072705471686100_bib65","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1085\/jgp.201010442","article-title":"Fatty acid modulation and polyamine block of GluK2 kainate receptors analyzed by scanning mutagenesis","volume":"136","author":"Wilding","year":"2010","journal-title":"J. Gen. Physiol."},{"key":"2023072705471686100_bib66","doi-asserted-by":"publisher","first-page":"3349:1\u201310","DOI":"10.1038\/ncomms4349","article-title":"Radial symmetry in a chimeric glutamate receptor pore","volume":"5","author":"Wilding","year":"2014","journal-title":"Nat. Commun."},{"key":"2023072705471686100_bib67","doi-asserted-by":"publisher","first-page":"5973","DOI":"10.1523\/JNEUROSCI.20-16-05973.2000","article-title":"The Lurcher mutation identifies \u03b4 2 as an AMPA\/kainate receptor-like channel that is potentiated by Ca(2+)","volume":"20","author":"Wollmuth","year":"2000","journal-title":"J. Neurosci."},{"key":"2023072705471686100_bib68","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.neuron.2016.08.012","article-title":"Structural bases of noncompetitive inhibition of AMPA-subtype ionotropic glutamate receptors by antiepileptic drugs","volume":"91","author":"Yelshanskaya","year":"2016","journal-title":"Neuron."},{"key":"2023072705471686100_bib69","doi-asserted-by":"publisher","first-page":"1050:1\u201312","DOI":"10.1038\/s41598-017-01146-z","article-title":"Role of the ion channel extracellular collar in AMPA receptor gating","volume":"7","author":"Yelshanskaya","year":"2017","journal-title":"Sci. Rep."},{"key":"2023072705471686100_bib70","doi-asserted-by":"publisher","first-page":"29708","DOI":"10.1074\/jbc.M414215200","article-title":"Conserved structural and functional control of N-methyl-D-aspartate receptor gating by transmembrane domain M3","volume":"280","author":"Yuan","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2023072705471686100_bib71","doi-asserted-by":"publisher","first-page":"5237","DOI":"10.1073\/pnas.1500953112","article-title":"Cadmium-cysteine coordination in the BK inner pore region and its structural and functional implications","volume":"112","author":"Zhou","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072705471686100_bib72","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/42009","article-title":"Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor gene","volume":"388","author":"Zuo","year":"1997","journal-title":"Nature."}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/151\/4\/435\/1800647\/jgp_201812234.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/151\/4\/435\/1800647\/jgp_201812234.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T07:23:17Z","timestamp":1775287397000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/151\/4\/435\/124292\/Cadmium-opens-GluK2-kainate-receptors-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,29]]},"references-count":72,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.201812234","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,29]]}}}