{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:46:29Z","timestamp":1793357189085,"version":"4.5.0"},"reference-count":60,"publisher":"American Society for Clinical Investigation","issue":"18","funder":[{"name":"National Institute of Health","award":["HL135749"],"award-info":[{"award-number":["HL135749"]}]},{"name":"National Institute of Health","award":["HL10880"],"award-info":[{"award-number":["HL10880"]}]},{"name":"National Institute of Health","award":["HL122662"],"award-info":[{"award-number":["HL122662"]}]},{"name":"National Institute of Health","award":["HL122358"],"award-info":[{"award-number":["HL122358"]}]},{"name":"National Institute of Health","award":["HL101681"],"award-info":[{"award-number":["HL101681"]}]},{"name":"National Institute of Health","award":["OD008396"],"award-info":[{"award-number":["OD008396"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["16EIA26720006"],"award-info":[{"award-number":["16EIA26720006"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["17SDG33660149"],"award-info":[{"award-number":["17SDG33660149"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MCW NRC\/AHW","award":["#9520217"],"award-info":[{"award-number":["#9520217"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,21]]},"abstract":"<jats:p>\n                    Supplementing diets with high potassium helps reduce hypertension in humans. Inwardly rectifying K\n                    <jats:sup>+<\/jats:sup>\n                    channels K\n                    <jats:sub>ir<\/jats:sub>\n                    4.1 (\n                    <jats:italic>Kcnj10<\/jats:italic>\n                    ) and K\n                    <jats:sub>ir<\/jats:sub>\n                    5.1 (\n                    <jats:italic>Kcnj16<\/jats:italic>\n                    ) are highly expressed in the basolateral membrane of distal renal tubules and contribute to Na\n                    <jats:sup>+<\/jats:sup>\n                    reabsorption and K\n                    <jats:sup>+<\/jats:sup>\n                    secretion through the direct control of transepithelial voltage. To define the importance of K\n                    <jats:sub>ir<\/jats:sub>\n                    5.1 in blood pressure control under conditions of salt-induced hypertension, we generated a\n                    <jats:italic>Kcnj16<\/jats:italic>\n                    knockout in Dahl salt-sensitive (SS) rats (SS\n                    <jats:sup>Kcnj16\u2013\/\u2013<\/jats:sup>\n                    ). SS\n                    <jats:sup>Kcnj16\u2013\/\u2013<\/jats:sup>\n                    rats exhibited hypokalemia and reduced blood pressure, and when fed a high-salt diet (4% NaCl), experienced 100% mortality within a few days triggered by salt wasting and severe hypokalemia. Electrophysiological recordings of basolateral K\n                    <jats:sup>+<\/jats:sup>\n                    channels in the collecting ducts isolated from SS\n                    <jats:sup>Kcnj16\u2013\/\u2013<\/jats:sup>\n                    rats revealed activity of only homomeric K\n                    <jats:sub>ir<\/jats:sub>\n                    4.1 channels. K\n                    <jats:sub>ir<\/jats:sub>\n                    4.1 expression was upregulated in SS\n                    <jats:sup>Kcnj16\u2013\/\u2013<\/jats:sup>\n                    rats, but the protein was predominantly localized in the cytosol in SS\n                    <jats:sup>Kcnj16\u2013\/\u2013<\/jats:sup>\n                    rats. Benzamil, but not hydrochlorothiazide or furosemide, rescued this phenotype from mortality on a high-salt diet. Supplementation of high-salt diet with increased potassium (2% KCl) prevented mortality in SS\n                    <jats:sup>Kcnj16\u2013\/\u2013<\/jats:sup>\n                    rats and prevented or mitigated hypertension in SS\n                    <jats:sup>Kcnj16\u2013\/\u2013<\/jats:sup>\n                    or control SS rats, respectively. Our results demonstrate that K\n                    <jats:sub>ir<\/jats:sub>\n                    5.1 channels are key regulators of renal salt handling in SS hypertension.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.92331","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T11:00:49Z","timestamp":1505905249000},"source":"Crossref","is-referenced-by-count":102,"title":["Essential role of Kir5.1 channels in renal salt handling and blood pressure control"],"prefix":"10.1172","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3680-5527","authenticated-orcid":true,"given":"Oleg","family":"Palygin","sequence":"first","affiliation":[{"name":"Department of Physiology and"},{"name":"Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Levchenko","sequence":"additional","affiliation":[{"name":"Department of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria V.","family":"Ilatovskaya","sequence":"additional","affiliation":[{"name":"Department of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengis S.","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Department of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleh M.","family":"Pochynyuk","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Texas Health Science Center Medical School, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Physiology and"},{"name":"Human and Molecular Genetics Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron M.","family":"Geurts","sequence":"additional","affiliation":[{"name":"Department of 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