{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:52:38Z","timestamp":1787496758946,"version":"build-2736575974"},"reference-count":67,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK136462"],"award-info":[{"award-number":["DK136462"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK119170"],"award-info":[{"award-number":["DK119170"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["EIA35260097"],"award-info":[{"award-number":["EIA35260097"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24POST1191738"],"award-info":[{"award-number":["24POST1191738"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24SCEFIA1259812"],"award-info":[{"award-number":["24SCEFIA1259812"]}],"id":[{"id":"10.13039\/100000968","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":[[2025,5,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Maintaining systemic Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    homeostasis plays a critical yet underappreciated role in setting the baseline and salt sensitivity of blood pressure. ClC\u2010K2 Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    \u2010permeable channel is localized on the basolateral membrane of the distal nephron segments. Impaired NaCl reabsorption in the thick ascending limb and distal convoluted tubule has been proposed as the underlying cause of polyuria and hypotension in patients with the Bartter's syndrome type 3 due to loss\u2010of\u2010function of the channel. However, the relevance of ClC\u2010K2 in the collecting duct intercalated cells (ICs) for renal function and Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    homeostasis remains obscure. Here, we compared the systemic manifestations and examined signaling components in ClC\u2010K2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    Pax8 (lacking ClC\u2010K2 in renal nephron) and ClC\u2010K2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    B1 ATPase (lacking ClC\u2010K2 in ICs) mice. ClC\u2010K2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    Pax8 mice exhibited hypotension, reduced glomerular filtration rate, urinary NaCl wasting, and metabolic alkalosis with hypokalemia, thereby recapitulating the phenotype of Bartter's syndrome. While ClC\u2010K2 deletion in ICs did not affect urinary volume and baseline blood pressure, ClC\u2010K2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    B1 ATPase mice developed moderate hypotension in response to dietary Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    deficiency. Decreased expression and impaired apical translocation of pendrin (\n                    <jats:italic>Slc26A4<\/jats:italic>\n                    ) were causative for the augmented urinary Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    excretion. Furthermore, ClC\u2010K2 deletion in ICs interfered with the development of Angiotensin II\u2010dependent hypertension. The reduced pendrin function, along with a compensatory upregulation of the epithelial Na\n                    <jats:sup>+<\/jats:sup>\n                    channel, caused hypokalemic metabolic alkalosis in ClC\u2010K2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    B1 ATPase mice. In summary, we show that ClC\u2010K2 activity in ICs of the collecting duct plays physiologically relevant roles in the regulation of systemic Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    balance and acid\u2013base homeostasis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500588rr","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T10:50:11Z","timestamp":1747219811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intercalated Cell ClC\u2010K2 Channel Contributes to Systemic Cl\n                    <sup>\u2212<\/sup>\n                    Balance and Acid\u2013Base Homeostasis"],"prefix":"10.1096","volume":"39","author":[{"given":"Anna","family":"Atamanchuk","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyrylo","family":"Pyrshev","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Kordysh","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Zaika","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-6897","authenticated-orcid":false,"given":"Oleh","family":"Pochynyuk","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2063193"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpu060"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/65.2.606S"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00241-0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/143471"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00056.2003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccl.2016.12.002"},{"key":"e_1_2_10_9_1","article-title":"Effects of Low Sodium Diet Versus High Sodium Diet on Blood Pressure, Renin, Aldosterone, Catecholamines, Cholesterol, and Triglyceride","volume":"12","author":"Graudal N. 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