{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:38:12Z","timestamp":1768901892223,"version":"3.49.0"},"reference-count":28,"publisher":"The Company of Biologists","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"crossref","award":["04464"],"award-info":[{"award-number":["04464"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP 142469"],"award-info":[{"award-number":["MOP 142469"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Lactate is produced in most vertebrate cells as a by-product of anaerobic metabolism. In addition to its role as a fuel for many tissues, circulating lactate can act as a signalling molecule and stimulates ventilation in air- and water-breathing vertebrates. Recent evidence suggests lactate acts on O2- and CO2\/H+-sensitive chemoreceptors located in the mammalian carotid body. While analogous receptors (neuroepithelial cells or NECs) in fish gills are presumed to also function as lactate sensors, direct evidence is lacking. Here, using ratiometric Fura-2 Ca2+ imaging, we show that chemosensitive NECs isolated from killifish gills respond to lactate (5\u201310\u2005mmol\u2005l\u22121; pHe \u223c7.8) with intracellular Ca2+ elevations. These responses were inhibited by an L-type Ca2+ channel blocker (nifedipine; 0.5\u2005\u00b5mol\u00a0l\u22121), a monocarboxylic acid transporter (MCT) blocker (\u03b1-cyano-4-hydroxycinnamate; 300\u2005\u00b5mol\u00a0l\u22121) or a competitive MCT substrate (pyruvate; 5\u2005mmol\u2005l\u22121). These data provide the first direct evidence that gill NECs act as lactate sensors.<\/jats:p>","DOI":"10.1242\/jeb.245088","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T10:10:25Z","timestamp":1669284625000},"source":"Crossref","is-referenced-by-count":10,"title":["Lactate sensing by neuroepithelial cells isolated from the gills of killifish (<i>Fundulus heteroclitus<\/i>)"],"prefix":"10.1242","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-5437","authenticated-orcid":false,"given":"Erin M.","family":"Leonard","sequence":"first","affiliation":[{"name":"Wilfred Laurier University 1 Department of Biology , , Waterloo, ON , Canada , N2L 3C5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona E.","family":"Weaver","sequence":"additional","affiliation":[{"name":"McMaster University 2 Department of Biology , , Hamilton, ON , Canada , L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin A.","family":"Nurse","sequence":"additional","affiliation":[{"name":"McMaster University 2 Department of Biology , , Hamilton, ON , Canada , L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"2023010910133592500_JEB245088C1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s00424-014-1514-2","article-title":"Extracellular H+ induces Ca2+ signals in respiratory chemoreceptors of zebrafish","volume":"467","author":"Abdallah","year":"2015","journal-title":"Pflugers Arch."},{"key":"2023010910133592500_JEB245088C2","doi-asserted-by":"publisher","first-page":"111054","DOI":"10.1016\/j.cbpa.2021.111054","article-title":"Rapid and reversible modulation of blood haemoglobin content during diel cycles of hypoxia in killifish (Fundulus heteroclitus)","volume":"261","author":"Borowiec","year":"2021","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"2023010910133592500_JEB245088C3","doi-asserted-by":"publisher","first-page":"101454","DOI":"10.1016\/j.redox.2020.101454","article-title":"Lactate as a fulcrum of metabolism","volume":"35","author":"Brooks","year":"2020","journal-title":"Redox Biol."},{"key":"2023010910133592500_JEB245088C4","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/nature15721","article-title":"Oxygen regulation of breathing through an olfactory receptor activated by lactate","volume":"527","author":"Chang","year":"2015","journal-title":"Nature"},{"key":"2023010910133592500_JEB245088C5","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1242\/jeb.015248","article-title":"A comparative analysis of putative oxygen-sensing cells in the fish gill","volume":"211","author":"Coolidge","year":"2008","journal-title":"J. Exp. 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(1985)"},{"key":"2023010910133592500_JEB245088C8","doi-asserted-by":"publisher","first-page":"e21231","DOI":"10.7554\/eLife.21231","article-title":"Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes","volume":"6","author":"Hockman","year":"2017","journal-title":"Elife"},{"key":"2023010910133592500_JEB245088C9","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nature24057","article-title":"Glucose feeds the TCA cycle via circulating lactate","volume":"551","author":"Hui","year":"2017","journal-title":"Nature"},{"key":"2023010910133592500_JEB245088C10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cne.10680","article-title":"Neuroepithelial cells and associated innervation of the zebrafish gill: a confocal immunofluorescence study","volume":"461","author":"Jonz","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"2023010910133592500_JEB245088C11","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1113\/jphysiol.2004.069294","article-title":"Neuroepithelial oxygen chemoreceptors of the zebrafish gill","volume":"560","author":"Jonz","year":"2004","journal-title":"J. Physiol."},{"key":"2023010910133592500_JEB245088C12","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/cphy.c100069","article-title":"Peripheral chemoreceptors: function and plasticity of the carotid body","volume":"2","author":"Kumar","year":"2012","journal-title":"Compr Physiol"},{"key":"2023010910133592500_JEB245088C13","doi-asserted-by":"publisher","first-page":"5434","DOI":"10.3390\/ijms21155434","article-title":"Expanding role of dopaminergic inhibition in hypercapnic responses of cultured rat carotid body cells: involvement of type II glial cells","volume":"21","author":"Leonard","year":"2020","journal-title":"Int. J. Mol. 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