{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:54:01Z","timestamp":1790232841180,"version":"4.1.0"},"reference-count":81,"publisher":"Society for Neuroscience","issue":"21","license":[{"start":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T00:00:00Z","timestamp":1542931200000},"content-version":"vor","delay-in-days":204,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2018,5,23]]},"abstract":"<jats:p>Neuronal nicotinic acetylcholine receptors (nAChRs) are pentamers built from a variety of subunits. Some are homomeric assemblies of \u03b1 subunits, others heteromeric assemblies of \u03b1 and \u03b2 subunits which can adopt two stoichiometries (2\u03b1:3\u03b2 or 3\u03b1:2\u03b2). There is evidence for the presence of heteromeric nAChRs with the two stoichiometries in the CNS, but it has not yet been possible to identify them at a given synapse. The 2\u03b1:3\u03b2 receptors are highly sensitive to agonists, whereas the 3\u03b1:2\u03b2 stoichiometric variants, initially described as low sensitivity receptors, are indeed activated by low and high concentrations of ACh. We have taken advantage of the discovery that two compounds (NS9283 and Zn) potentiate selectively the 3\u03b1:2\u03b2 nAChRs to establish (in mice of either sex) the presence of these variants at the motoneuron-Renshaw cell (MN-RC) synapse. NS9283 prolonged the decay of the two-component EPSC mediated by heteromeric nAChRs. NS9283 and Zn also prolonged spontaneous EPSCs involving heteromeric nAChRs, and one could rule out prolongations resulting from AChE inhibition by NS9283. These results establish the presence of 3\u03b1:2\u03b2 nAChRs at the MN-RC synapse. At the functional level, we had previously explained the duality of the EPSC by assuming that high ACh concentrations in the synaptic cleft account for the fast component and that spillover of ACh accounts for the slow component. The dual ACh sensitivity of 3\u03b1:2\u03b2 nAChRs now allows to attribute to these receptors both components of the EPSC.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>Heteromeric nicotinic receptors assemble \u03b1 and \u03b2 subunits in pentameric structures, which can adopt two stoichiometries: 3\u03b1:2\u03b2 or 2\u03b1:3\u03b2. Both stoichiometric variants are present in the CNS, but they have never been located and characterized functionally at the level of an identified synapse. Our data indicate that 3\u03b1:2\u03b2 receptors are present at the spinal cord synapses between motoneurons and Renshaw cells, where their dual mode of activation (by high concentrations of ACh for synaptic receptors, by low concentrations of ACh for extrasynaptic receptors) likely accounts for the biphasic character of the synaptic current. More generally, 3\u03b1:2\u03b2 nicotinic receptors appear unique by their capacity to operate both in the cleft of classical synapses and at extrasynaptic locations.<\/jats:p>","DOI":"10.1523\/jneurosci.0070-18.2018","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T16:09:19Z","timestamp":1525363759000},"page":"4943-4956","source":"Crossref","is-referenced-by-count":21,"title":["Stoichiometry of the Heteromeric Nicotinic Receptors of the Renshaw Cell"],"prefix":"10.1523","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4221-7526","authenticated-orcid":false,"given":"Boris","family":"Lamotte d'Incamps","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6367-8690","authenticated-orcid":false,"given":"Tamara","family":"Zorbaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Dingova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8564-0290","authenticated-orcid":false,"given":"Eric","family":"Krejci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3964-0796","authenticated-orcid":false,"given":"Philippe","family":"Ascher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2018,5,3]]},"reference":[{"key":"2023041803311206000_38.21.4943.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.06.024"},{"key":"2023041803311206000_38.21.4943.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0115-12.2012"},{"key":"2023041803311206000_38.21.4943.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.08.024"},{"key":"2023041803311206000_38.21.4943.4","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12268"},{"key":"2023041803311206000_38.21.4943.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3565-12.2012"},{"key":"2023041803311206000_38.21.4943.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079653"},{"key":"2023041803311206000_38.21.4943.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2008.00104.x"},{"key":"2023041803311206000_38.21.4943.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2016.05.019"},{"key":"2023041803311206000_38.21.4943.9","unstructured":"Cornish-Bowden A (2012) Fundamentals of enzyme kinetics, Ed 4. 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