{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:11:29Z","timestamp":1787220689825,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in <jats:italic>PKD1<\/jats:italic> and <jats:italic>PKD2<\/jats:italic> cause autosomal dominant polycystic kidney disease (ADPKD), which is characterized by the formation of fluid\u2010filled cysts in the kidney. In a subset of ADPKD patients, reduced blood calcium (Ca<jats:sup>2+<\/jats:sup>) and magnesium (Mg<jats:sup>2+<\/jats:sup>) concentrations are observed. As cystic fluid contains increased ATP concentrations and purinergic signaling reduces electrolyte reabsorption, we hypothesized that inhibiting ATP release could normalize blood Ca<jats:sup>2+<\/jats:sup> and Mg<jats:sup>2+<\/jats:sup> levels in ADPKD. Inducible kidney\u2010specific <jats:italic>Pkd1<\/jats:italic> knockout mice (iKsp\u2010<jats:italic>Pkd1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) exhibit hypocalcemia and hypomagnesemia in a precystic stage and show increased expression of the ATP\u2010release channel pannexin\u20101. Therefore, we administered the pannexin\u20101 inhibitor brilliant blue\u2010FCF (BB\u2010FCF) every other day from Day 3 to 28 post\u2010induction of <jats:italic>Pkd1<\/jats:italic> gene inactivation. On Day 29, both serum Ca<jats:sup>2+<\/jats:sup> and Mg<jats:sup>2+<\/jats:sup> concentrations were reduced in iKsp\u2010<jats:italic>Pkd1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, while urinary Ca<jats:sup>2+<\/jats:sup> and Mg<jats:sup>2+<\/jats:sup> excretion was similar between the genotypes. However, serum and urinary levels of Ca<jats:sup>2+<\/jats:sup> and Mg<jats:sup>2+<\/jats:sup> were unaltered by BB\u2010FCF treatment, regardless of genotype. BB\u2010FCF did significantly decrease gene expression of the ion channels <jats:italic>Trpm6<\/jats:italic> and <jats:italic>Trpv5<\/jats:italic> in both control and iKsp\u2010<jats:italic>Pkd1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Finally, no renoprotective effects of BB\u2010FCF treatment were observed in iKsp\u2010<jats:italic>Pkd1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Thus, administration of BB\u2010FCF failed to normalize serum Ca<jats:sup>2+<\/jats:sup> and Mg<jats:sup>2+<\/jats:sup> levels.<\/jats:p>","DOI":"10.14814\/phy2.15956","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T01:44:10Z","timestamp":1712022250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of pannexin\u20101 does not restore electrolyte balance in precystic <i>Pkd1<\/i> knockout mice"],"prefix":"10.14814","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7786-4021","authenticated-orcid":false,"given":"Wouter H.","family":"van Megen","sequence":"first","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun J.","family":"van Houtert","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caro","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien J. M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen H. F.","family":"de Baaij","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1816-8544","authenticated-orcid":false,"given":"Joost G. 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