{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:56:52Z","timestamp":1790528212260,"version":"4.1.0"},"reference-count":57,"publisher":"Society for Neuroscience","issue":"1","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eNeuro"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Transient receptor potential channel, TRPM4, the putative molecular substrate for Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated nonselective cation current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>CAN<\/jats:sub>\n                    ), is hypothesized to generate bursting activity of pre-B\u00f6tzinger complex (pre-B\u00f6tC) inspiratory neurons and critically contribute to respiratory rhythmogenesis. Another TRP channel, TRPC3, which mediates Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    fluxes, may be involved in regulating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -related signaling, including affecting TRPM4\/\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>CAN<\/jats:sub>\n                    in respiratory pre-B\u00f6tC neurons. However, TRPM4 and TRPC3 expression in pre-B\u00f6tC inspiratory neurons and functional roles of these channels remain to be determined. By single-cell multiplex RT-PCR, we show mRNA expression for these channels in pre-B\u00f6tC inspiratory neurons in rhythmically active medullary\n                    <jats:italic>in vitro<\/jats:italic>\n                    slices from neonatal rats and mice. Functional contributions were analyzed with pharmacological inhibitors of TRPM4 or TRPC3\n                    <jats:italic>in vitro<\/jats:italic>\n                    as well as in mature rodent arterially perfused\n                    <jats:italic>in situ<\/jats:italic>\n                    brainstem\u2013spinal cord preparations. Perturbations of respiratory circuit activity were also compared with those by a blocker of\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>CAN<\/jats:sub>\n                    . Pharmacologically attenuating endogenous activation of TRPM4, TRPC3, or\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>CAN<\/jats:sub>\n                    <jats:italic>in vitro<\/jats:italic>\n                    similarly reduced the amplitude of inspiratory motoneuronal activity without significant perturbations of inspiratory frequency or variability of the rhythm. Amplitude perturbations were correlated with reduced inspiratory glutamatergic pre-B\u00f6tC neuronal activity, monitored by multicellular dynamic calcium imaging\n                    <jats:italic>in vitro.<\/jats:italic>\n                    In more intact circuits\n                    <jats:italic>in situ<\/jats:italic>\n                    , the reduction of pre-B\u00f6tC and motoneuronal inspiratory activity amplitude was accompanied by reduced post-inspiratory motoneuronal activity, without disruption of rhythm generation. We conclude that endogenously activated TRPM4, which likely mediates\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>CAN<\/jats:sub>\n                    , and TRPC3 channels in pre-B\u00f6tC inspiratory neurons play fundamental roles in respiratory pattern formation but are not critically involved in respiratory rhythm generation.\n                  <\/jats:p>","DOI":"10.1523\/eneuro.0332-17.2018","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T20:35:13Z","timestamp":1517430913000},"page":"ENEURO.0332-17.2018","source":"Crossref","is-referenced-by-count":36,"title":["Transient Receptor Potential Channels TRPM4 and TRPC3 Critically Contribute to Respiratory Motor Pattern Formation but not Rhythmogenesis in Rodent Brainstem Circuits"],"prefix":"10.1523","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7747-3434","authenticated-orcid":false,"given":"Hidehiko","family":"Koizumi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6825-7166","authenticated-orcid":false,"given":"Tibin T.","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2530-767X","authenticated-orcid":false,"given":"Justine X.","family":"Chia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad F.","family":"Tariq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan S.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Mosher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9017-827X","authenticated-orcid":false,"given":"Yonghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2952-8779","authenticated-orcid":false,"given":"Naohiro","family":"Koshiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7676-4643","authenticated-orcid":false,"given":"Jeffrey C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2018,1,31]]},"reference":[{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.268136"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.08.016"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07156.x"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094928"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04855.x"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.6","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1152\/jn.1999.82.1.382","article-title":"Models of respiratory rhythm generation in the pre-B\u00f6tzinger complex. I. Bursting pacemaker neurons","volume":"82","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.7","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1152\/jn.1999.82.1.398","article-title":"Models of respiratory rhythm generation in the pre-B\u00f6tzinger complex. II. Populations Of coupled pacemaker neurons","volume":"82","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.8","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-013-2103-4"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.9","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.134577"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.10","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-53613-6.00008-3"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2237-04.2005"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.12","doi-asserted-by":"publisher","DOI":"10.1007\/s10827-010-0311-y"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.13","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1871"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1309531110"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.15","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01377.2010"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2707-07.2007"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.17","doi-asserted-by":"publisher","DOI":"10.1038\/nn0901-927"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.18","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00004.2010"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.01.012"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.20","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12582"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00431-7"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.22","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12042"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808793106"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3916-07.2008"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3553-07.2008"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4427-12.2013"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.27","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0081-16.2016"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.28","doi-asserted-by":"publisher","DOI":"10.1038\/22540"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00719-5"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.30","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0011-16.2016"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.31","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.149021"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.32","doi-asserted-by":"publisher","DOI":"10.1177\/1073858408329510"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.33","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.237362"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3040-09.2010"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.35","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.154765"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.36","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1523\/JNEUROSCI.23-04-01478.2003","article-title":"A novel functional neuron group for respiratory rhythm generation in the ventral medulla","volume":"23","year":"2003","journal-title":"J Neurosci"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06540.x"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.38","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.133660"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.39","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(95)00147-6"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.06.023"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2006.01.011"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.42","doi-asserted-by":"publisher","DOI":"10.1007\/s10867-011-9214-z"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.43","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12301"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.44","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00035.2013"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808776106"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.46","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90958.2008"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.47","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63274-6.00001-1"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.48","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3015"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.49","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63274-6.00002-3"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.50","doi-asserted-by":"publisher","DOI":"10.1540\/jsmr.38.39"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.51","doi-asserted-by":"publisher","DOI":"10.1126\/science.1683005"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.52","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00985.2007"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.03.002"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.54","doi-asserted-by":"crossref","unstructured":"Teulon J (2000) Ca2+ Activated Nonselective Cation Channels. Berlin: Springer.","DOI":"10.1007\/978-3-642-57083-4_25"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.55","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.1.104"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.56","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1996.271.1.H244"},{"key":"2023041302123292000_5.1.ENEURO.0332-17.2018.57","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.193037"}],"container-title":["eneuro"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/ENEURO.0332-17.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T05:41:37Z","timestamp":1681364497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eneuro.org\/lookup\/doi\/10.1523\/ENEURO.0332-17.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,3,8]]},"published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1523\/ENEURO.0332-17.2018"],"URL":"https:\/\/doi.org\/10.1523\/eneuro.0332-17.2018","relation":{},"ISSN":["2373-2822"],"issn-type":[{"value":"2373-2822","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]}}}