{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:58:33Z","timestamp":1790078313267,"version":"4.0.1"},"reference-count":140,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ivermectin (IVM) is a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. By activating invertebrate pentameric glutamate-gated chloride channels (GluCl receptors; GluClRs), IVM induces sustained chloride influx and long-lasting membrane hyperpolarization that inhibit neural excitation in nematodes. Although IVM activates the<jats:italic>C. elegans<\/jats:italic>heteromeric GluCl\u03b1\/\u03b2 receptor, it cannot activate a homomeric receptor composed of the<jats:italic>C. elegans<\/jats:italic>GluCl\u03b2 subunits. To understand this incapability, we generated a homopentameric \u03b17-GluCl\u03b2 chimeric receptor that consists of an extracellular ligand-binding domain of an \u03b17 nicotinic acetylcholine receptor known to be potentiated by IVM, and a chloride-selective channel domain assembled from GluCl\u03b2 subunits. Application of IVM prior to acetylcholine inhibited the responses of the chimeric \u03b17-GluCl\u03b2R. Adding IVM to activated \u03b17-GluCl\u03b2Rs, considerably accelerated the decline of ACh-elicited currents and stabilized the receptors in a non-conducting state. Determination of IVM association and dissociation rate constants and recovery experiments suggest that, following initial IVM binding to open \u03b17-GluCl\u03b2Rs, the drug induces a conformational change and locks the ion channel in a closed state for a long duration. We further found that IVM also inhibits the activation by glutamate of a homomeric receptor assembled from the<jats:italic>C. elegans<\/jats:italic>full-length GluCl\u03b2 subunits.<\/jats:p>","DOI":"10.1038\/srep42481","type":"journal-article","created":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T10:26:13Z","timestamp":1487586373000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization"],"prefix":"10.1038","volume":"7","author":[{"given":"Nurit","family":"Degani-Katzav","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moran","family":"Har-Even","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revital","family":"Gortler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruthi","family":"Tobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Paas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,20]]},"reference":[{"key":"BFsrep42481_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.2183\/pjab.87.13","volume":"87","author":"A Crump","year":"2011","unstructured":"Crump, A. & Omura, S. Ivermectin, \u2018wonder drug\u2019 from Japan: the human use perspective. Proc Jpn Acad Ser B Phys Biol Sci 87, 13\u201328 (2011).","journal-title":"Proc Jpn Acad Ser B Phys Biol Sci"},{"key":"BFsrep42481_CR2","doi-asserted-by":"publisher","first-page":"853","DOI":"10.2174\/138920112800399095","volume":"13","author":"WC Campbell","year":"2012","unstructured":"Campbell, W. C. History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. Curr Pharm Biotechnol 13, 853\u2013865 (2012).","journal-title":"Curr Pharm Biotechnol"},{"key":"BFsrep42481_CR3","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.pt.2005.08.014","volume":"21","author":"TG Geary","year":"2005","unstructured":"Geary, T. G. Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol 21, 530\u2013532 (2005).","journal-title":"Trends Parasitol"},{"key":"BFsrep42481_CR4","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/371707a0","volume":"371","author":"DF Cully","year":"1994","unstructured":"Cully, D. F. et al. Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371, 707\u2013711 (1994).","journal-title":"Nature"},{"key":"BFsrep42481_CR5","doi-asserted-by":"publisher","first-page":"16035","DOI":"10.1074\/jbc.271.27.16035","volume":"271","author":"A Etter","year":"1996","unstructured":"Etter, A., Cully, D. F., Schaeffer, J. M., Liu, K. K. & Arena, J. P. An amino acid substitution in the pore region of a glutamate-gated chloride channel enables the coupling of ligand binding to channel gating. J Biol Chem 271, 16035\u201316039 (1996).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR6","doi-asserted-by":"publisher","first-page":"5867","DOI":"10.1093\/emboj\/16.19.5867","volume":"16","author":"JA Dent","year":"1997","unstructured":"Dent, J. A., Davis, M. W. & Avery, L. avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBO J 16, 5867\u20135879 (1997).","journal-title":"EMBO J"},{"key":"BFsrep42481_CR7","doi-asserted-by":"publisher","first-page":"33167","DOI":"10.1074\/jbc.272.52.33167","volume":"272","author":"DK Vassilatis","year":"1997","unstructured":"Vassilatis, D. K. et al. Genetic and biochemical evidence for a novel avermectin-sensitive chloride channel in Caenorhabditis elegans. Isolation and characterization. J Biol Chem 272, 33167\u201333174 (1997).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0014-5793(02)03245-3","volume":"528","author":"P Li","year":"2002","unstructured":"Li, P., Slimko, E. M. & Lester, H. A. Selective elimination of glutamate activation and introduction of fluorescent proteins into a Caenorhabditis elegans chloride channel. FEBS Lett 528, 77\u201382 (2002).","journal-title":"FEBS Lett"},{"key":"BFsrep42481_CR9","doi-asserted-by":"publisher","first-page":"7373","DOI":"10.1523\/JNEUROSCI.22-17-07373.2002","volume":"22","author":"EM Slimko","year":"2002","unstructured":"Slimko, E. M., McKinney, S., Anderson, D. J., Davidson, N. & Lester, H. A. Selective electrical silencing of mammalian neurons in vitro by the use of invertebrate ligand-gated chloride channels. J Neurosci 22, 7373\u20137379 (2002).","journal-title":"J Neurosci"},{"key":"BFsrep42481_CR10","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.molbiopara.2006.02.003","volume":"147","author":"A Cook","year":"2006","unstructured":"Cook, A. et al. Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors. Mol Biochem Parasitol 147, 118\u2013125 (2006).","journal-title":"Mol Biochem Parasitol"},{"key":"BFsrep42481_CR11","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1006\/expr.1993.1064","volume":"77","author":"TG Geary","year":"1993","unstructured":"Geary, T. G. et al. Haemonchus contortus: ivermectin-induced paralysis of the pharynx. Exp Parasitol 77, 88\u201396 (1993).","journal-title":"Exp Parasitol"},{"key":"BFsrep42481_CR12","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1017\/S0031182097001601","volume":"115","author":"DJ Brownlee","year":"1997","unstructured":"Brownlee, D. J., Holden-Dye, L. & Walker, R. J. Actions of the anthelmintic ivermectin on the pharyngeal muscle of the parasitic nematode, Ascaris suum. Parasitology 115 (Pt 5), 553\u2013561 (1997).","journal-title":"Parasitology"},{"key":"BFsrep42481_CR13","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1073\/pnas.97.6.2674","volume":"97","author":"JA Dent","year":"2000","unstructured":"Dent, J. A., Smith, M. M., Vassilatis, D. K. & Avery, L. The genetics of ivermectin resistance in Caenorhabditis elegans. Proc Natl Acad Sci USA 97, 2674\u20132679 (2000).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR14","doi-asserted-by":"publisher","first-page":"20120","DOI":"10.1073\/pnas.1011983107","volume":"107","author":"Y Moreno","year":"2010","unstructured":"Moreno, Y., Nabhan, J. F., Solomon, J., Mackenzie, C. D. & Geary, T. G. Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. Proc Natl Acad Sci USA 107, 20120\u201320125 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR15","doi-asserted-by":"publisher","first-page":"866","DOI":"10.2174\/138920112800399077","volume":"13","author":"TG Geary","year":"2012","unstructured":"Geary, T. G. & Moreno, Y. Macrocyclic lactone anthelmintics: spectrum of activity and mechanism of action. Curr Pharm Biotechnol 13, 866\u2013872 (2012).","journal-title":"Curr Pharm Biotechnol"},{"key":"BFsrep42481_CR16","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s10158-016-0190-7","volume":"16","author":"AJ Wolstenholme","year":"2016","unstructured":"Wolstenholme, A. J., Maclean, M. J., Coates, R., McCoy, C. J. & Reaves, B. J. How do the macrocyclic lactones kill filarial nematode larvae? Invert Neurosci 16, 7 (2016).","journal-title":"Invert Neurosci"},{"key":"BFsrep42481_CR17","doi-asserted-by":"publisher","first-page":"40232","DOI":"10.1074\/jbc.R112.406280","volume":"287","author":"AJ Wolstenholme","year":"2012","unstructured":"Wolstenholme, A. J. Glutamate-gated chloride channels. J Biol Chem 287, 40232\u201340238 (2012).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR18","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nrn731","volume":"3","author":"A Karlin","year":"2002","unstructured":"Karlin, A. Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci 3, 102\u2013114 (2002).","journal-title":"Nat Rev Neurosci"},{"key":"BFsrep42481_CR19","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.tins.2004.04.002","volume":"27","author":"HA Lester","year":"2004","unstructured":"Lester, H. A., Dibas, M. I., Dahan, D. S., Leite, J. F. & Dougherty, D. A. Cys-loop receptors: new twists and turns. Trends Neurosci 27, 329\u2013336 (2004).","journal-title":"Trends Neurosci"},{"key":"BFsrep42481_CR20","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.bcp.2007.07.038","volume":"74","author":"P Taylor","year":"2007","unstructured":"Taylor, P. et al. Structure-guided drug design: conferring selectivity among neuronal nicotinic receptor and acetylcholine-binding protein subtypes. Biochem Pharmacol 74, 1164\u20131171 (2007).","journal-title":"Biochem Pharmacol"},{"key":"BFsrep42481_CR21","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nrd2927","volume":"8","author":"A Taly","year":"2009","unstructured":"Taly, A., Corringer, P. J., Guedin, D., Lestage, P. & Changeux, J. P. Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat Rev Drug Discov 8, 733\u2013750 (2009).","journal-title":"Nat Rev Drug Discov"},{"key":"BFsrep42481_CR22","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1038\/nn.3197","volume":"15","author":"T Boulin","year":"2012","unstructured":"Boulin, T. et al. Positive modulation of a Cys-loop acetylcholine receptor by an auxiliary transmembrane subunit. Nat Neurosci 15, 1374\u20131381 (2012).","journal-title":"Nat Neurosci"},{"key":"BFsrep42481_CR23","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1152\/physrev.00015.2011","volume":"92","author":"SM Sine","year":"2012","unstructured":"Sine, S. M. End-plate acetylcholine receptor: structure, mechanism, pharmacology, and disease. Physiol Rev 92, 1189\u20131234 (2012).","journal-title":"Physiol Rev"},{"key":"BFsrep42481_CR24","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.tips.2014.12.002","volume":"36","author":"KT Dineley","year":"2015","unstructured":"Dineley, K. T., Pandya, A. A. & Yakel, J. L. Nicotinic ACh receptors as therapeutic targets in CNS disorders. Trends Pharmacol Sci 36, 96\u2013108 (2015).","journal-title":"Trends Pharmacol Sci"},{"key":"BFsrep42481_CR25","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.bcp.2015.07.028","volume":"97","author":"A Chatzidaki","year":"2015","unstructured":"Chatzidaki, A. & Millar, N. S. Allosteric modulation of nicotinic acetylcholine receptors. Biochem Pharmacol 97, 408\u2013417 (2015).","journal-title":"Biochem Pharmacol"},{"key":"BFsrep42481_CR26","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.tips.2015.05.002","volume":"36","author":"C Stokes","year":"2015","unstructured":"Stokes, C., Treinin, M. & Papke, R. L. Looking below the surface of nicotinic acetylcholine receptors. Trends Pharmacol Sci 36, 514\u2013523 (2015).","journal-title":"Trends Pharmacol Sci"},{"key":"BFsrep42481_CR27","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1124\/mol.116.104240","volume":"90","author":"J Corradi","year":"2016","unstructured":"Corradi, J. & Bouzat, C. Understanding the Bases of Function and Modulation of alpha7 Nicotinic Receptors: Implications for Drug Discovery. Mol Pharmacol 90, 288\u2013299 (2016).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR28","doi-asserted-by":"publisher","first-page":"40239","DOI":"10.1074\/jbc.R112.406496","volume":"287","author":"SC Lummis","year":"2012","unstructured":"Lummis, S. C. 5-HT(3) receptors. J Biol Chem 287, 40239\u201340245 (2012).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR29","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/embor.2012.189","volume":"14","author":"D Kesters","year":"2013","unstructured":"Kesters, D. et al. Structural basis of ligand recognition in 5-HT3 receptors. EMBO Rep 14, 49\u201356 (2013).","journal-title":"EMBO Rep"},{"key":"BFsrep42481_CR30","doi-asserted-by":"publisher","first-page":"S67","DOI":"10.1016\/j.psyneuen.2009.08.010","volume":"34","author":"NN Zheleznova","year":"2009","unstructured":"Zheleznova, N. N., Sedelnikova, A. & Weiss, D. S. Function and modulation of \u03b4-containing GABAA receptors. Psychoneuroendocrinology 34, S67\u2013S73 (2009).","journal-title":"Psychoneuroendocrinology"},{"key":"BFsrep42481_CR31","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1097\/ALN.0b013e3182315d93","volume":"115","author":"G Akk","year":"2011","unstructured":"Akk, G. & Steinbach, J. H. Structural studies of the actions of anesthetic drugs on the gamma-aminobutyric acid type A receptor. Anesthesiology 115, 1338\u20131348 (2011).","journal-title":"Anesthesiology"},{"key":"BFsrep42481_CR32","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1038\/aps.2014.50","volume":"35","author":"J Liang","year":"2014","unstructured":"Liang, J. & Olsen, R. W. Alcohol use disorders and current pharmacological therapies: the role of GABA(A) receptors. Acta Pharmacol Sin 35, 981\u2013993 (2014).","journal-title":"Acta Pharmacol Sin"},{"key":"BFsrep42481_CR33","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/bs.apha.2014.10.006","volume":"72","author":"S Seljeset","year":"2015","unstructured":"Seljeset, S., Laverty, D. & Smart, T. G. Inhibitory neurosteroids and the GABAA receptor. Adv Pharmacol 72, 165\u2013187 (2015).","journal-title":"Adv Pharmacol"},{"key":"BFsrep42481_CR34","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1002\/1439-7633(20021104)3:11<1042::AID-CBIC1042>3.0.CO;2-7","volume":"3","author":"HG Breitinger","year":"2002","unstructured":"Breitinger, H. G. & Becker, C. M. The inhibitory glycine receptor-simple views of a complicated channel. Chembiochem 3, 1042\u20131052 (2002).","journal-title":"Chembiochem"},{"key":"BFsrep42481_CR35","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.tins.2004.04.010","volume":"27","author":"D Colquhoun","year":"2004","unstructured":"Colquhoun, D. & Sivilotti, L. G. Function and structure in glycine receptors and some of their relatives. Trends Neurosci 27, 337\u2013344 (2004).","journal-title":"Trends Neurosci"},{"key":"BFsrep42481_CR36","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1111\/j.1471-4159.2006.03908.x","volume":"97","author":"H Betz","year":"2006","unstructured":"Betz, H. & Laube, B. Glycine receptors: recent insights into their structural organization and functional diversity. J Neurochem. 97, 1600\u20131610 (2006).","journal-title":"J Neurochem."},{"key":"BFsrep42481_CR37","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.tig.2008.06.005","volume":"24","author":"RJ Harvey","year":"2008","unstructured":"Harvey, R. J., Topf, M., Harvey, K. & Rees, M. I. The genetics of hyperekplexia: more than startle! Trends Genet 24, 439\u2013447 (2008).","journal-title":"Trends Genet"},{"key":"BFsrep42481_CR38","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1113\/jphysiol.2009.178525","volume":"588","author":"LG Sivilotti","year":"2010","unstructured":"Sivilotti, L. G. What single-channel analysis tells us of the activation mechanism of ligand-gated channels: the case of the glycine receptor. J Physiol 588, 45\u201358 (2010).","journal-title":"J Physiol"},{"key":"BFsrep42481_CR39","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fnmol.2012.00060","volume":"5","author":"T Lynagh","year":"2012","unstructured":"Lynagh, T. & Lynch, J. W. Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin. Front Mol Neurosci 5, 60 (2012).","journal-title":"Front Mol Neurosci"},{"key":"BFsrep42481_CR40","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1111\/bph.12335","volume":"170","author":"N Schaefer","year":"2013","unstructured":"Schaefer, N., Langlhofer, G., Kluck, C. J. & Villmann, C. Glycine receptor mouse mutants: model systems for human hyperekplexia. Br J Pharmacol 170, 933\u2013952 (2013).","journal-title":"Br J Pharmacol"},{"key":"BFsrep42481_CR41","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/339704a0","volume":"339","author":"RC Hardie","year":"1989","unstructured":"Hardie, R. C. A histamine-activated chloride channel involved in neurotransmission at a photoreceptor synapse. Nature 339, 704\u2013706 (1989).","journal-title":"Nature"},{"key":"BFsrep42481_CR42","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nn787","volume":"5","author":"G Gisselmann","year":"2002","unstructured":"Gisselmann, G., Pusch, H., Hovemann, B. T. & Hatt, H. Two cDNAs coding for histamine-gated ion channels in D. melanogaster. Nat Neurosci 5, 11\u201312 (2002).","journal-title":"Nat Neurosci"},{"key":"BFsrep42481_CR43","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1074\/jbc.M107635200","volume":"277","author":"Y Zheng","year":"2002","unstructured":"Zheng, Y. et al. Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye. J. Biol. Chem. 277, 2000\u20132005 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFsrep42481_CR44","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/0014-2999(82)90133-9","volume":"77","author":"M Williams","year":"1982","unstructured":"Williams, M. & Risley, E. A. Interaction of avermectins with [3H]beta-carboline-3-carboxylate ethyl ester and [3H]diazepam binding sites in rat brain cortical membranes. Eur J Pharmacol 77, 307\u2013312 (1982).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep42481_CR45","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1111\/j.1471-4159.1985.tb08727.x","volume":"44","author":"RW Olsen","year":"1985","unstructured":"Olsen, R. W. & Snowman, A. M. Avermectin B1a modulation of gamma-aminobutyric acid\/benzodiazepine receptor binding in mammalian brain. J Neurochem 44, 1074\u20131082 (1985).","journal-title":"J Neurochem"},{"key":"BFsrep42481_CR46","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0026-895X(25)13064-2","volume":"32","author":"E Sigel","year":"1987","unstructured":"Sigel, E. & Baur, R. Effect of avermectin B1a on chick neuronal gamma-aminobutyrate receptor channels expressed in Xenopus oocytes. Mol Pharmacol 32, 749\u2013752 (1987).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR47","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/0014-2999(94)90500-2","volume":"259","author":"J Krusek","year":"1994","unstructured":"Krusek, J. & Zemkova, H. Effect of ivermectin on gamma-aminobutyric acid-induced chloride currents in mouse hippocampal embryonic neurones. Eur J Pharmacol 259, 121\u2013128 (1994).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep42481_CR48","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0014-2999(00)00164-3","volume":"394","author":"H Adelsberger","year":"2000","unstructured":"Adelsberger, H., Lepier, A. & Dudel, J. Activation of rat recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptor by the insecticide ivermectin. Eur J Pharmacol 394, 163\u2013170 (2000).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep42481_CR49","doi-asserted-by":"publisher","first-page":"12556","DOI":"10.1074\/jbc.M011264200","volume":"276","author":"Q Shan","year":"2001","unstructured":"Shan, Q., Haddrill, J. L. & Lynch, J. W. Ivermectin, an unconventional agonist of the glycine receptor chloride channel. J Biol Chem 276, 12556\u201312564 (2001).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR50","doi-asserted-by":"publisher","first-page":"27370","DOI":"10.1074\/jbc.M109.048405","volume":"284","author":"SA Pless","year":"2009","unstructured":"Pless, S. A. & Lynch, J. W. Magnitude of a conformational change in the glycine receptor beta1-beta2 loop is correlated with agonist efficacy. J Biol Chem 284, 27370\u201327376 (2009).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR51","doi-asserted-by":"crossref","unstructured":"Lynagh, T. & Lynch, J. W. Ivermectin binding sites in human and invertebrate Cys-loop receptors. Trends Pharmacol Sci (2012).","DOI":"10.1016\/j.tips.2012.05.002"},{"key":"BFsrep42481_CR52","doi-asserted-by":"publisher","first-page":"e1883","DOI":"10.1371\/journal.pntd.0001883","volume":"6","author":"C Menez","year":"2012","unstructured":"Menez, C., Sutra, J. F., Prichard, R. & Lespine, A. Relative neurotoxicity of ivermectin and moxidectin in Mdr1ab (-\/-) mice and effects on mammalian GABA(A) channel activity. PLoS Negl Trop Dis 6, e1883 (2012).","journal-title":"PLoS Negl Trop Dis"},{"key":"BFsrep42481_CR53","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.biocel.2011.11.005","volume":"44","author":"Q Wang","year":"2012","unstructured":"Wang, Q. & Lynch, J. W. A comparison of glycine- and ivermectin-mediated conformational changes in the glycine receptor ligand-binding domain. Int J Biochem Cell Biol 44, 335\u2013340 (2012).","journal-title":"Int J Biochem Cell Biol"},{"key":"BFsrep42481_CR54","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1124\/mol.53.2.283","volume":"53","author":"RM Krause","year":"1998","unstructured":"Krause, R. M. et al. Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. Mol Pharmacol 53, 283\u2013294 (1998).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR55","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1124\/mol.110.064295","volume":"78","author":"T Collins","year":"2010","unstructured":"Collins, T. & Millar, N. S. Nicotinic acetylcholine receptor transmembrane mutations convert ivermectin from a positive to a negative allosteric modulator. Mol Pharmacol 78, 198\u2013204 (2010).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR56","doi-asserted-by":"publisher","first-page":"7289","DOI":"10.1523\/JNEUROSCI.19-17-07289.1999","volume":"19","author":"BS Khakh","year":"1999","unstructured":"Khakh, B. S., Proctor, W. R., Dunwiddie, T. V., Labarca, C. & Lester, H. A. Allosteric control of gating and kinetics at P2X(4) receptor channels. J Neurosci 19, 7289\u20137299 (1999).","journal-title":"J Neurosci"},{"key":"BFsrep42481_CR57","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1085\/jgp.200308986","volume":"123","author":"A Priel","year":"2004","unstructured":"Priel, A. & Silberberg, S. D. Mechanism of ivermectin facilitation of human P2X4 receptor channels. J Gen Physiol 123, 281\u2013293 (2004).","journal-title":"J Gen Physiol"},{"key":"BFsrep42481_CR58","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.neuron.2007.03.020","volume":"54","author":"SD Silberberg","year":"2007","unstructured":"Silberberg, S. D., Li, M. & Swartz, K. J. Ivermectin Interaction with transmembrane helices reveals widespread rearrangements during opening of P2X receptor channels. Neuron 54, 263\u2013274 (2007).","journal-title":"Neuron"},{"key":"BFsrep42481_CR59","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neuropharm.2015.07.032","volume":"104","author":"C Habermacher","year":"2016","unstructured":"Habermacher, C., Dunning, K., Chataigneau, T. & Grutter, T. Molecular structure and function of P2X receptors. Neuropharmacology 104, 18\u201330 (2016).","journal-title":"Neuropharmacology"},{"key":"BFsrep42481_CR60","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/S0020-7519(03)00172-3","volume":"33","author":"DM Yates","year":"2003","unstructured":"Yates, D. M., Portillo, V. & Wolstenholme, A. J. The avermectin receptors of Haemonchus contortus and Caenorhabditis elegans. Int J Parasitol 33, 1183\u20131193 (2003).","journal-title":"Int J Parasitol"},{"key":"BFsrep42481_CR61","doi-asserted-by":"publisher","first-page":"8558","DOI":"10.1038\/srep08558","volume":"5","author":"T Lynagh","year":"2015","unstructured":"Lynagh, T. et al. Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels. Sci Rep 5, 8558 (2015).","journal-title":"Sci Rep"},{"key":"BFsrep42481_CR62","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0166-6851(98)00148-0","volume":"97","author":"NS Delany","year":"1998","unstructured":"Delany, N. S., Laughton, D. L. & Wolstenholme, A. J. Cloning and localisation of an avermectin receptor-related subunit from Haemonchus contortus. Mol Biochem Parasitol 97, 177\u2013187 (1998).","journal-title":"Mol Biochem Parasitol"},{"key":"BFsrep42481_CR63","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/S0166-6851(99)00120-6","volume":"103","author":"S Jagannathan","year":"1999","unstructured":"Jagannathan, S. et al. Ligand-gated chloride channel subunits encoded by the Haemonchus contortus and Ascaris suum orthologues of the Caenorhabditis elegans gbr-2 (avr-14) gene. Mol Biochem Parasitol 103, 129\u2013140 (1999).","journal-title":"Mol Biochem Parasitol"},{"key":"BFsrep42481_CR64","doi-asserted-by":"publisher","first-page":"e1003586","DOI":"10.1371\/journal.ppat.1003586","volume":"9","author":"V Dufour","year":"2013","unstructured":"Dufour, V., Beech, R. N., Wever, C., Dent, J. A. & Geary, T. G. Molecular cloning and characterization of novel glutamate-gated chloride channel subunits from Schistosoma mansoni. PLoS Pathog 9, e1003586 (2013).","journal-title":"PLoS Pathog"},{"key":"BFsrep42481_CR65","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.ijpddr.2014.07.004","volume":"4","author":"T Lynagh","year":"2014","unstructured":"Lynagh, T., Cromer, B. A., Dufour, V. & Laube, B. Comparative pharmacology of flatworm and roundworm glutamate-gated chloride channels: Implications for potential anthelmintics. Int J Parasitol Drugs Drug Resist 4, 244\u2013255 (2014).","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"BFsrep42481_CR66","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1111\/j.1365-2583.2006.00680.x","volume":"15","author":"Y Eguchi","year":"2006","unstructured":"Eguchi, Y. et al. Functional characterization of Musca glutamate- and GABA-gated chloride channels expressed independently and coexpressed in Xenopus oocytes. Insect Mol Biol 15, 773\u2013783 (2006).","journal-title":"Insect Mol Biol"},{"key":"BFsrep42481_CR67","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1653\/024.096.0358","volume":"96","author":"Y Dong","year":"2013","unstructured":"Dong, Y., Chen, Y., Wei, Q., Su, J. & Gao, C. Cloning and Polymorphism Analysis of Glutamate-Gated Chloride Channel Gene of Laodelphax striatellus (Hemiptera: Delphacidae). Florida Entomologist 96, 1168\u20131174 (2013).","journal-title":"Florida Entomologist"},{"key":"BFsrep42481_CR68","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1124\/mol.114.095869","volume":"86","author":"S Furutani","year":"2014","unstructured":"Furutani, S. et al. Exon 3 splicing and mutagenesis identify residues influencing cell surface density of heterologously expressed silkworm (Bombyx mori) glutamate-gated chloride channels. Mol Pharmacol 86, 686\u2013695 (2014).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ibmb.2013.11.004","volume":"45","author":"T Kita","year":"2014","unstructured":"Kita, T., Ozoe, F. & Ozoe, Y. Expression pattern and function of alternative splice variants of glutamate-gated chloride channel in the housefly Musca domestica. Insect Biochem Mol Biol 45, 1\u201310 (2014).","journal-title":"Insect Biochem Mol Biol"},{"key":"BFsrep42481_CR70","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1242\/jeb.118570","volume":"218","author":"JI Meyers","year":"2015","unstructured":"Meyers, J. I. et al. Characterization of the target of ivermectin, the glutamate-gated chloride channel, from Anopheles gambiae. J Exp Biol 218, 1478\u20131486 (2015).","journal-title":"J Exp Biol"},{"key":"BFsrep42481_CR71","doi-asserted-by":"crossref","unstructured":"Wu, S. F. et al. Expression pattern and pharmacological characterisation of two novel alternative splice variants of the glutamate-gated chloride channel in the small brown planthopper Laodelphax striatellus. Pest Manag Sci (2016).","DOI":"10.1002\/ps.4340"},{"key":"BFsrep42481_CR72","doi-asserted-by":"publisher","first-page":"e1004402","DOI":"10.1371\/journal.ppat.1004402","volume":"10","author":"I Cornejo","year":"2014","unstructured":"Cornejo, I. et al. Identification and functional expression of a glutamate- and avermectin-gated chloride channel from Caligus rogercresseyi, a southern Hemisphere sea louse affecting farmed fish. PLoS Pathog 10, e1004402 (2014).","journal-title":"PLoS Pathog"},{"key":"BFsrep42481_CR73","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s00239-009-9256-z","volume":"69","author":"J Kehoe","year":"2009","unstructured":"Kehoe, J. et al. Aplysia cys-loop glutamate-gated chloride channels reveal convergent evolution of ligand specificity. J Mol Evol 69, 125\u2013141 (2009).","journal-title":"J Mol Evol"},{"key":"BFsrep42481_CR74","doi-asserted-by":"publisher","first-page":"20187","DOI":"10.1074\/jbc.271.33.20187","volume":"271","author":"DF Cully","year":"1996","unstructured":"Cully, D. F., Paress, P. S., Liu, K. K., Schaeffer, J. M. & Arena, J. P. Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin. J Biol Chem 271, 20187\u201320191 (1996).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR75","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1124\/mol.108.053363","volume":"75","author":"S McCavera","year":"2009","unstructured":"McCavera, S., Rogers, A. T., Yates, D. M., Woods, D. J. & Wolstenholme, A. J. An ivermectin-sensitive glutamate-gated chloride channel from the parasitic nematode Haemonchus contortus. Mol Pharmacol 75, 1347\u20131355 (2009).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR76","doi-asserted-by":"crossref","unstructured":"Daeffler, K. N., Lester, H. A. & Dougherty, D. A. Functional Evaluation of Key Interactions Evident in the Structure of the Eukaryotic Cys-Loop Receptor GluCl. ACS Chem Biol (2014).","DOI":"10.1021\/cb500323d"},{"key":"BFsrep42481_CR77","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nature10139","volume":"474","author":"RE Hibbs","year":"2011","unstructured":"Hibbs, R. E. & Gouaux, E. Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474, 54\u201360 (2011).","journal-title":"Nature"},{"key":"BFsrep42481_CR78","doi-asserted-by":"publisher","first-page":"21029","DOI":"10.1074\/jbc.M112.423921","volume":"288","author":"SJ Frazier","year":"2013","unstructured":"Frazier, S. J., Cohen, B. N. & Lester, H. A. An engineered glutamate-gated chloride (GluCl) channel for sensitive, consistent neuronal silencing by ivermectin. J Biol Chem 288, 21029\u201321042 (2013).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR79","doi-asserted-by":"publisher","first-page":"E644","DOI":"10.1073\/pnas.1423753113","volume":"113","author":"N Degani-Katzav","year":"2016","unstructured":"Degani-Katzav, N., Gortler, R., Gorodetzki, L. & Paas, Y. Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel. Proc Natl Acad Sci USA 113, E644\u2013653 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR80","doi-asserted-by":"publisher","first-page":"14875","DOI":"10.1074\/jbc.M511657200","volume":"281","author":"M Sunesen","year":"2006","unstructured":"Sunesen, M. et al. Mechanism of Cl- selection by a glutamate-gated chloride (GluCl) receptor revealed through mutations in the selectivity filter. J Biol Chem 281, 14875\u201314881 (2006).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR81","doi-asserted-by":"publisher","first-page":"43830","DOI":"10.1074\/jbc.M111.282715","volume":"286","author":"DD Bar-Lev","year":"2011","unstructured":"Bar-Lev, D. D., Degani-Katzav, N., Perelman, A. & Paas, Y. Molecular dissection of Cl\u2013selective Cys-loop receptor points to components that are dispensable or essential for channel activity. J Biol Chem 286, 43830\u201343841 (2011).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR82","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0166-6851(03)00102-6","volume":"129","author":"SG Forrester","year":"2003","unstructured":"Forrester, S. G., Prichard, R. K., Dent, J. A. & Beech, R. N. Haemonchus contortus: HcGluCla expressed in Xenopus oocytes forms a glutamate-gated ion channel that is activated by ibotenate and the antiparasitic drug ivermectin. Mol Biochem Parasitol 129, 115\u2013121 (2003).","journal-title":"Mol Biochem Parasitol"},{"key":"BFsrep42481_CR83","doi-asserted-by":"publisher","first-page":"10213","DOI":"10.1523\/JNEUROSCI.19-23-10213.1999","volume":"19","author":"AJ Boileau","year":"1999","unstructured":"Boileau, A. J. & Czajkowski, C. Identification of transduction elements for benzodiazepine modulation of the GABA(A) receptor: three residues are required for allosteric coupling. J Neurosci 19, 10213\u201310220 (1999).","journal-title":"J Neurosci"},{"key":"BFsrep42481_CR84","doi-asserted-by":"publisher","first-page":"43002","DOI":"10.1074\/jbc.M206321200","volume":"277","author":"AK Bera","year":"2002","unstructured":"Bera, A. K., Chatav, M. & Akabas, M. H. GABA(A) receptor M2-M3 loop secondary structure and changes in accessibility during channel gating. J Biol Chem 277, 43002\u201343010 (2002).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR85","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nature01280","volume":"421","author":"TL Kash","year":"2003","unstructured":"Kash, T. L., Jenkins, A., Kelley, J. C., Trudell, J. R. & Harrison, N. L. Coupling of agonist binding to channel gating in the GABA(A) receptor. Nature 421, 272\u2013275 (2003).","journal-title":"Nature"},{"key":"BFsrep42481_CR86","doi-asserted-by":"publisher","first-page":"50151","DOI":"10.1074\/jbc.M305357200","volume":"278","author":"NL Absalom","year":"2003","unstructured":"Absalom, N. L., Lewis, T. M., Kaplan, W., Pierce, K. D. & Schofield, P. R. Role of charged residues in coupling ligand binding and channel activation in the extracellular domain of the glycine receptor. J Biol Chem 278, 50151\u201350157 (2003).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR87","doi-asserted-by":"publisher","first-page":"5621","DOI":"10.1074\/jbc.M114.616573","volume":"290","author":"S Scott","year":"2015","unstructured":"Scott, S., Lynch, J. W. & Keramidas, A. Correlating structural and energetic changes in glycine receptor activation. J Biol Chem 290, 5621\u20135634 (2015).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR88","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nature04130","volume":"438","author":"SC Lummis","year":"2005","unstructured":"Lummis, S. C. et al. Cis-trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel. Nature 438, 248\u2013252 (2005).","journal-title":"Nature"},{"key":"BFsrep42481_CR89","doi-asserted-by":"publisher","first-page":"9358","DOI":"10.1523\/JNEUROSCI.1045-05.2005","volume":"25","author":"DC Reeves","year":"2005","unstructured":"Reeves, D. C., Jansen, M., Bali, M., Lemster, T. & Akabas, M. H. A role for the beta 1-beta 2 loop in the gating of 5-HT3 receptors. J Neurosci 25, 9358\u20139366 (2005).","journal-title":"J Neurosci"},{"key":"BFsrep42481_CR90","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1111\/j.1471-4159.2009.06180.x","volume":"110","author":"IM Paulsen","year":"2009","unstructured":"Paulsen, I. M., Martin, I. L. & Dunn, S. M. Isomerization of the proline in the M2-M3 linker is not required for activation of the human 5-HT3A receptor. J Neurochem 110, 870\u2013878 (2009).","journal-title":"J Neurochem"},{"key":"BFsrep42481_CR91","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1085\/jgp.200709856","volume":"130","author":"A Jha","year":"2007","unstructured":"Jha, A., Cadugan, D. J., Purohit, P. & Auerbach, A. Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and M2-M3 linker. J Gen Physiol 130, 547\u2013558 (2007).","journal-title":"J Gen Physiol"},{"key":"BFsrep42481_CR92","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1523\/JNEUROSCI.6185-08.2009","volume":"29","author":"WY Lee","year":"2009","unstructured":"Lee, W. Y., Free, C. R. & Sine, S. M. Binding to gating transduction in nicotinic receptors: Cys-loop energetically couples to pre-M1 and M2-M3 regions. J Neurosci 29, 3189\u20133199 (2009).","journal-title":"J Neurosci"},{"key":"BFsrep42481_CR93","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1523\/JNEUROSCI.4121-08.2009","volume":"29","author":"RE Wiltfong","year":"2009","unstructured":"Wiltfong, R. E. & Jansen, M. Probing protein packing surrounding the residues in and flanking the nicotinic acetylcholine receptor M2M3 loop. J Neurosci 29, 1626\u20131635 (2009).","journal-title":"J Neurosci"},{"key":"BFsrep42481_CR94","doi-asserted-by":"publisher","first-page":"6642","DOI":"10.1074\/jbc.M411048200","volume":"280","author":"F Sala","year":"2005","unstructured":"Sala, F., Mulet, J., Sala, S., Gerber, S. & Criado, M. Charged amino acids of the N-terminal domain are involved in coupling binding and gating in alpha7 nicotinic receptors. J Biol Chem 280, 6642\u20136647 (2005).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR95","doi-asserted-by":"publisher","first-page":"6813","DOI":"10.1073\/pnas.0407739102","volume":"102","author":"RJ Law","year":"2005","unstructured":"Law, R. J., Henchman, R. H. & McCammon, J. A. A gating mechanism proposed from a simulation of a human alpha7 nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 102, 6813\u20136818 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR96","doi-asserted-by":"publisher","first-page":"25331","DOI":"10.1074\/jbc.M111.221754","volume":"286","author":"J Zhang","year":"2011","unstructured":"Zhang, J. et al. Desensitization of alpha7 nicotinic receptor is governed by coupling strength relative to gate tightness. J Biol Chem 286, 25331\u201325340 (2011).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR97","doi-asserted-by":"publisher","first-page":"18207","DOI":"10.1073\/pnas.0509024102","volume":"102","author":"T Grutter","year":"2005","unstructured":"Grutter, T. et al. Molecular tuning of fast gating in pentameric ligand-gated ion channels. Proc Natl Acad Sci USA 102, 18207\u201318212 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR98","doi-asserted-by":"publisher","first-page":"7808","DOI":"10.1523\/JNEUROSCI.0448-08.2008","volume":"28","author":"C Bouzat","year":"2008","unstructured":"Bouzat, C., Bartos, M., Corradi, J. & Sine, S. M. The interface between extracellular and transmembrane domains of homomeric Cys-loop receptors governs open-channel lifetime and rate of desensitization. J Neurosci 28, 7808\u20137819 (2008).","journal-title":"J Neurosci"},{"key":"BFsrep42481_CR99","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/0896-6273(90)90344-F","volume":"5","author":"S Couturier","year":"1990","unstructured":"Couturier, S. et al. A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX. Neuron 5, 847\u2013856 (1990).","journal-title":"Neuron"},{"key":"BFsrep42481_CR100","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/353846a0","volume":"353","author":"F Revah","year":"1991","unstructured":"Revah, F. et al. Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor. Nature 353, 846\u2013849 (1991).","journal-title":"Nature"},{"key":"BFsrep42481_CR101","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/S0026-895X(25)10029-1","volume":"45","author":"X Peng","year":"1994","unstructured":"Peng, X., Katz, M., Gerzanich, V., Anand, R. & Lindstrom, J. Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes. Mol Pharmacol 45, 546\u2013554 (1994).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR102","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1093\/emboj\/21.5.1012","volume":"21","author":"S Halevi","year":"2002","unstructured":"Halevi, S. et al. The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors. EMBO J 21, 1012\u20131020 (2002).","journal-title":"EMBO J"},{"key":"BFsrep42481_CR103","doi-asserted-by":"publisher","first-page":"34411","DOI":"10.1074\/jbc.M300170200","volume":"278","author":"S Halevi","year":"2003","unstructured":"Halevi, S. et al. Conservation within the RIC-3 gene family. Effectors of mammalian nicotinic acetylcholine receptor expression. J Biol Chem 278, 34411\u201334417 (2003).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR104","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1113\/jphysiol.2007.149492","volume":"586","author":"EA Gay","year":"2008","unstructured":"Gay, E. A., Giniatullin, R., Skorinkin, A. & Yakel, J. L. Aromatic residues at position 55 of rat alpha7 nicotinic acetylcholine receptors are critical for maintaining rapid desensitization. J Physiol 586, 1105\u20131115 (2008).","journal-title":"J Physiol"},{"key":"BFsrep42481_CR105","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1089\/adt.2007.120","volume":"6","author":"R Roncarati","year":"2008","unstructured":"Roncarati, R. et al. Functional properties of alpha7 nicotinic acetylcholine receptors co-expressed with RIC-3 in a stable recombinant CHO-K1 cell line. Assay Drug Dev Technol 6, 181\u2013193 (2008).","journal-title":"Assay Drug Dev Technol"},{"key":"BFsrep42481_CR106","doi-asserted-by":"publisher","first-page":"20819","DOI":"10.1073\/pnas.1315775110","volume":"110","author":"N Andersen","year":"2013","unstructured":"Andersen, N., Corradi, J., Sine, S. M. & Bouzat, C. Stoichiometry for activation of neuronal alpha7 nicotinic receptors. Proc Natl Acad Sci USA 110, 20819\u201320824 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR107","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.neuropharm.2016.02.032","volume":"107","author":"ND Andersen","year":"2016","unstructured":"Andersen, N. D. et al. Exploring the positive allosteric modulation of human \u03b17 nicotinic receptors from a single-channel perspective. Neuropharmacology 107, 189\u2013200 (2016).","journal-title":"Neuropharmacology"},{"key":"BFsrep42481_CR108","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.neuropharm.2015.04.010","volume":"95","author":"H Yan","year":"2015","unstructured":"Yan, H. et al. The coupling interface and pore domain codetermine the single-channel activity of the alpha7 nicotinic receptor. Neuropharmacology 95, 448\u2013458 (2015).","journal-title":"Neuropharmacology"},{"key":"BFsrep42481_CR109","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.neuropharm.2011.07.035","volume":"61","author":"T Collins","year":"2011","unstructured":"Collins, T., Young, G. T. & Millar, N. S. Competitive binding at a nicotinic receptor transmembrane site of two alpha7-selective positive allosteric modulators with differing effects on agonist-evoked desensitization. Neuropharmacology 61, 1306\u20131313 (2011).","journal-title":"Neuropharmacology"},{"key":"BFsrep42481_CR110","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1124\/mol.110.066662","volume":"78","author":"J Wang","year":"2010","unstructured":"Wang, J., Horenstein, N. A., Stokes, C. & Papke, R. L. Tethered agonist analogs as site-specific probes for domains of the human alpha7 nicotinic acetylcholine receptor that differentially regulate activation and desensitization. Mol Pharmacol 78, 1012\u20131025 (2010).","journal-title":"Mol Pharmacol"},{"key":"BFsrep42481_CR111","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1085\/jgp.201110674","volume":"138","author":"U Karlsson","year":"2011","unstructured":"Karlsson, U., Druzin, M. & Johansson, S. Cl(-) concentration changes and desensitization of GABA(A) and glycine receptors. J Gen Physiol 138, 609\u2013626 (2011).","journal-title":"J Gen Physiol"},{"key":"BFsrep42481_CR112","unstructured":"Hille, B. Ion channels of excitable membranes. (Sinauer Associates, Inc., 2001)."},{"key":"BFsrep42481_CR113","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/BF02780343","volume":"4","author":"EL Ochoa","year":"1990","unstructured":"Ochoa, E. L., Li, L. & McNamee, M. G. Desensitization of central cholinergic mechanisms and neuroadaptation to nicotine. Mol Neurobiol 4, 251\u2013287 (1990).","journal-title":"Mol Neurobiol"},{"key":"BFsrep42481_CR114","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/37120","volume":"390","author":"VI Pidoplichko","year":"1997","unstructured":"Pidoplichko, V. I., DeBiasi, M., Williams, J. T. & Dani, J. A. Nicotine activates and desensitizes midbrain dopamine neurons. Nature 390, 401\u2013404 (1997).","journal-title":"Nature"},{"key":"BFsrep42481_CR115","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1113\/jphysiol.2003.053447","volume":"553","author":"KG Paradiso","year":"2003","unstructured":"Paradiso, K. G. & Steinbach, J. H. Nicotine is highly effective at producing desensitization of rat alpha4beta2 neuronal nicotinic receptors. J Physiol 553, 857\u2013871 (2003).","journal-title":"J Physiol"},{"key":"BFsrep42481_CR116","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.tins.2005.04.009","volume":"28","author":"R Giniatullin","year":"2005","unstructured":"Giniatullin, R., Nistri, A. & Yakel, J. L. Desensitization of nicotinic ACh receptors: shaping cholinergic signaling. Trends Neurosci 28, 371\u2013378 (2005).","journal-title":"Trends Neurosci"},{"key":"BFsrep42481_CR117","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1111\/j.1469-7793.1999.0657u.x","volume":"516","author":"ME Nelson","year":"1999","unstructured":"Nelson, M. E. & Lindstrom, J. Single channel properties of human alpha3 AChRs: impact of beta2, beta4 and alpha5 subunits. J Physiol 516 (Pt 3), 657\u2013678 (1999).","journal-title":"J Physiol"},{"key":"BFsrep42481_CR118","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1113\/jphysiol.2006.114645","volume":"576","author":"J Wu","year":"2006","unstructured":"Wu, J. et al. Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors. J Physiol 576, 103\u2013118 (2006).","journal-title":"J Physiol"},{"key":"BFsrep42481_CR119","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1124\/jpet.103.048777","volume":"305","author":"L Zhao","year":"2003","unstructured":"Zhao, L. et al. Functional properties of homomeric, human alpha 7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 human epithelial cell line. J Pharmacol Exp Ther 305, 1132\u20131141 (2003).","journal-title":"J Pharmacol Exp Ther"},{"key":"BFsrep42481_CR120","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1017\/S0031182000063812","volume":"104","author":"RJ Martin","year":"1992","unstructured":"Martin, R. J. & Kusel, J. R. On the distribution of a fluorescent ivermectin probe (4\u201d 5,7 dimethyl-bodipy proprionylivermectin) in Ascaris membranes. Parasitology 104 (Pt 3), 549\u2013555 (1992).","journal-title":"Parasitology"},{"key":"BFsrep42481_CR121","doi-asserted-by":"publisher","first-page":"10145","DOI":"10.1016\/S0021-9258(18)82184-6","volume":"268","author":"DE Warnock","year":"1993","unstructured":"Warnock, D. E. et al. Determination of plasma membrane lipid mass and composition in cultured Chinese hamster ovary cells using high gradient magnetic affinity chromatography. J Biol Chem 268, 10145\u201310153 (1993).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR122","first-page":"59","volume":"72","author":"DD Oehler","year":"1989","unstructured":"Oehler, D. D. & Miller, J. A. Liquid chromatographic determination of ivermectin in bovine serum. J Assoc Off Anal Chem 72, 59 (1989).","journal-title":"J Assoc Off Anal Chem"},{"key":"BFsrep42481_CR123","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1111\/jnc.1999.72.1.318","volume":"72","author":"A Etter","year":"1999","unstructured":"Etter, A. et al. Picrotoxin blockade of invertebrate glutamate-gated chloride channels: subunit dependence and evidence for binding within the pore. J Neurochem 72, 318\u2013326 (1999).","journal-title":"J Neurochem"},{"key":"BFsrep42481_CR124","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/366479a0","volume":"366","author":"JL Eisele","year":"1993","unstructured":"Eisele, J. L. et al. Chimaeric nicotinic-serotonergic receptor combines distinct ligand binding and channel specificities. Nature 366, 479\u2013483 (1993).","journal-title":"Nature"},{"key":"BFsrep42481_CR125","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1085\/jgp.107.3.369","volume":"107","author":"A Figl","year":"1996","unstructured":"Figl, A., Labarca, C., Davidson, N., Lester, H. A. & Cohen, B. N. Voltage-jump relaxation kinetics for wild-type and chimeric beta subunits of neuronal nicotinic receptors. J Gen Physiol 107, 369\u2013379 (1996).","journal-title":"J Gen Physiol"},{"key":"BFsrep42481_CR126","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1038\/nature02753","volume":"430","author":"C Bouzat","year":"2004","unstructured":"Bouzat, C. et al. Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel. Nature 430, 896\u2013900 (2004).","journal-title":"Nature"},{"key":"BFsrep42481_CR127","doi-asserted-by":"publisher","first-page":"15877","DOI":"10.1073\/pnas.0507599102","volume":"102","author":"Y Paas","year":"2005","unstructured":"Paas, Y. et al. Pore conformations and gating mechanism of a Cys-loop receptor. Proc Natl Acad Sci USA 102, 15877\u201315882 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR128","doi-asserted-by":"publisher","first-page":"26519","DOI":"10.1074\/jbc.M110.102327","volume":"285","author":"I Pittel","year":"2010","unstructured":"Pittel, I., Witt-Kehati, D., Degani-Katzav, N. & Paas, Y. Probing pore constriction in a ligand-gated ion channel by trapping a metal ion in the pore upon agonist dissociation. J Biol Chem 285, 26519\u201326531 (2010).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR129","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1085\/jgp.201511478","volume":"146","author":"N Schmandt","year":"2015","unstructured":"Schmandt, N. et al. A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways of activation. J Gen Physiol 146, 323\u2013340 (2015).","journal-title":"J Gen Physiol"},{"key":"BFsrep42481_CR130","doi-asserted-by":"publisher","first-page":"42821","DOI":"10.1074\/jbc.M306978200","volume":"278","author":"CS Chang","year":"2003","unstructured":"Chang, C. S., Olcese, R. & Olsen, R. W. A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation. J Biol Chem 278, 42821\u201342828 (2003).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR131","doi-asserted-by":"publisher","first-page":"46583","DOI":"10.1074\/jbc.M308974200","volume":"278","author":"XQ Hu","year":"2003","unstructured":"Hu, X. Q., Zhang, L., Stewart, R. R. & Weight, F. F. Arginine 222 in the pre-transmembrane domain 1 of 5-HT3A receptors links agonist binding to channel gating. J Biol Chem 278, 46583\u201346589 (2003).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR132","doi-asserted-by":"publisher","first-page":"27304","DOI":"10.1074\/jbc.M109.023598","volume":"284","author":"DI Perkins","year":"2009","unstructured":"Perkins, D. I. et al. Loop 2 Structure in Glycine and GABAA Receptors Plays a Key Role in Determining Ethanol sensitivity J Biol Chem 284, 27304\u201327314 (2009).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR133","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1021\/bi901550p","volume":"49","author":"IH Yamodo","year":"2010","unstructured":"Yamodo, I. H., Chiara, D. C., Cohen, J. B. & Miller, K. W. Conformational changes in the nicotinic acetylcholine receptor during gating and desensitization. Biochemistry 49, 156\u2013165 (2010).","journal-title":"Biochemistry"},{"key":"BFsrep42481_CR134","doi-asserted-by":"publisher","first-page":"35129","DOI":"10.1074\/jbc.M111.269027","volume":"286","author":"SA Pless","year":"2011","unstructured":"Pless, S. A., Leung, A. W., Galpin, J. D. & Ahern, C. A. Contributions of conserved residues at the gating interface of glycine receptors. J Biol Chem 286, 35129\u201335136 (2011).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR135","doi-asserted-by":"publisher","first-page":"18716","DOI":"10.1073\/pnas.1313156110","volume":"110","author":"G Gonzalez-Gutierrez","year":"2013","unstructured":"Gonzalez-Gutierrez, G., Cuello, L. G., Nair, S. K. & Grosman, C. Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography. Proc Natl Acad Sci USA 110, 18716\u201318721 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep42481_CR136","doi-asserted-by":"publisher","first-page":"e1002393","DOI":"10.1371\/journal.pbio.1002393","volume":"14","author":"C Bertozzi","year":"2016","unstructured":"Bertozzi, C., Zimmermann, I., Engeler, S., Hilf, R. J. & Dutzler, R. Signal Transduction at the Domain Interface of Prokaryotic Pentameric Ligand-Gated Ion Channels. PLoS Biol 14, e1002393 (2016).","journal-title":"PLoS Biol"},{"key":"BFsrep42481_CR137","doi-asserted-by":"publisher","first-page":"43913","DOI":"10.1074\/jbc.M111.262634","volume":"286","author":"T Lynagh","year":"2011","unstructured":"Lynagh, T., Webb, T. I., Dixon, C. L., Cromer, B. A. & Lynch, J. W. Molecular determinants of ivermectin sensitivity at the glycine receptor chloride channel. J Biol Chem 286, 43913\u201343924 (2011).","journal-title":"J Biol Chem"},{"key":"BFsrep42481_CR138","doi-asserted-by":"publisher","first-page":"e95072","DOI":"10.1371\/journal.pone.0095072","volume":"9","author":"G Hernando","year":"2014","unstructured":"Hernando, G. & Bouzat, C. Caenorhabditis elegans neuromuscular junction: GABA receptors and ivermectin action. PLoS One 9, e95072 (2014).","journal-title":"PLoS One"},{"key":"BFsrep42481_CR139","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1016\/0006-2952(73)90196-2","volume":"22","author":"Y Cheng","year":"1973","unstructured":"Cheng, Y. & Prusoff, W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22, 3099\u20133108 (1973).","journal-title":"Biochem Pharmacol"},{"key":"BFsrep42481_CR140","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/nature14853","volume":"526","author":"J Du","year":"2015","unstructured":"Du, J., Lu, W., Wu, S., Cheng, Y. & Gouaux, E. Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature 526, 224\u2013229 (2015).","journal-title":"Nature"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep42481","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42481.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep42481.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T14:26:50Z","timestamp":1749997610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep42481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,20]]},"references-count":140,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3,15]]}},"alternative-id":["BFsrep42481"],"URL":"https:\/\/doi.org\/10.1038\/srep42481","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,20]]},"assertion":[{"value":"5 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"42481"}}