{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:59:36Z","timestamp":1778943576109,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T00:00:00Z","timestamp":1546473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL007852"],"award-info":[{"award-number":["HL007852"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL122358"],"award-info":[{"award-number":["HL122358"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL135749"],"award-info":[{"award-number":["HL135749"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Acute and chronic homeostatic pH regulation is critical for the maintenance of optimal cellular function. Renal mechanisms dominate global pH regulation over longer time frames, and rapid adjustments in ventilation compensate for acute pH and CO\n 2<\/jats:sub>\n changes. Ventilatory CO\n 2<\/jats:sub>\n and pH chemoreflexes are primarily determined by brain chemoreceptors with intrinsic pH sensitivity likely driven by K\n +<\/jats:sup>\n channels. Here, we studied acute and chronic pH regulation in\n Kcnj 16<\/jats:italic>\n mutant Dahl salt\u2010sensitive (SS\n \n Kcnj16\u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n ) rats;\n Kcnj16<\/jats:italic>\n encodes the pH\u2010sensitive inwardly rectifying K\n +<\/jats:sup>\n 5.1 (Kir5.1) channel. SS\n \n Kcnj16\u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n rats hyperventilated at rest, likely compensating for a chronic metabolic acidosis. Despite their resting hyperventilation, SS\n \n Kcnj16\u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n ) rats showed up to 45% reduction in the ventilatory response to graded hypercapnic acidosis\n vs<\/jats:italic>\n . controls. SS\n \n Kcnj16\u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n rats chronically treated with bicarbonate or the carbonic anhydrase inhibitor hydrochlorothiazide had partial restoration of arterial pH, but there was a further reduction in the ventilatory response to hypercapnic acidosis. SS\n \n Kcnj16\u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n rats also had a nearly absent hypoxic ventilatory response, suggesting major contributions of Kir5.1 to O\n 2<\/jats:sub>\n \u2010 and CO\n 2<\/jats:sub>\n \u2010dependent chemoreflexes. Although previous studies demonstrated beneficial effects of a high\u2010K\n +<\/jats:sup>\n diet (HKD) on cardiorenal phenotypes in SS\n \n Kcnj16\u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n rats, HKD failed to restore the observed ventilatory phenotypes. We conclude that Kir5.1 is a key regulator of renal H\n +<\/jats:sup>\n handling and essential for acute and chronic regulation of arterial pH as determinants of the ventilatory CO\n 2<\/jats:sub>\n chemoreflex.\u2014Puissant, M. M., Muere, C.., Levchenko, V., Manis, A. D., Martino, P., Forster, H. V., Palygin, O., Staruschenko, A., Hodges, M. R. Genetic mutation of\n Kcnj16<\/jats:italic>\n identifies Kir5.1\u2010containing channels as key regulators of acute and chronic pH homeostasis. FASEB J. 33, 5067\u20135075 (2019).\n www.fasebj.org<\/jats:ext-link>\n <\/jats:p>","DOI":"10.1096\/fj.201802257r","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T12:38:06Z","timestamp":1546519086000},"page":"5067-5075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Genetic mutation of\n Kcnj16<\/i>\n identifies Kir5.1\u2010containing channels as key regulators of acute and chronic pH homeostasis"],"prefix":"10.1096","volume":"33","author":[{"given":"Madeleine M.","family":"Puissant","sequence":"first","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa","family":"Muere","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladislav","family":"Levchenko","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna D.","family":"Manis","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Martino","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Department of Biology Carthage College Kenosha Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert V.","family":"Forster","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg","family":"Palygin","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Neuroscience Research Center Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Staruschenko","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R.","family":"Hodges","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Neuroscience Research Center Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1965.208.3.436"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00112.2008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00282.2004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1409"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1357"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fncel.2017.00034","article-title":"Identifying candidate genes that underlie cellular pH sensitivity in serotonin neurons using transcriptomics: a potential role for Kir5.1 channels","volume":"11","author":"Puissant M. 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