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Higher energy expenditure in AC6\u2212\/\u2212 relative to wild-type (WT) mice, was associated with lower urinary pH, mild alkalosis in conjunction with elevated blood HCO3\u2212 concentrations, and significantly higher renal abundance of the H+-ATPase B1 subunit. In contrast with WT mice, AC6\u2212\/\u2212 mice have a less pronounced increase in urinary pH after 8 days of HCO3\u2212 challenge, which is associated with increased blood pH and HCO3\u2212 concentrations. Immunohistochemistry demonstrated that AC6 was expressed in intercalated cells (IC), but subcellular distribution of the H+-ATPase B1 subunit, pendrin, and the anion exchangers 1 and 2 in AC6\u2212\/\u2212 mice was normal. In the AC6\u2212\/\u2212 mice, H+-ATPase B1 subunit levels after HCO3\u2212 challenge were greater, which correlated with a higher number of type A IC. In contrast with the AC6\u2212\/\u2212 mice, AC6loxloxPax8Cre mice had normal urinary pH under baseline conditions but higher blood HCO3\u2212 than controls after HCO3\u2212 challenge. In conclusion, AC6 is required for maintaining normal acid\u2013base homeostasis and energy expenditure. Under baseline conditions, renal AC6 is redundant for acid\u2013base balance but becomes important under alkaline conditions.<\/jats:p>","DOI":"10.1042\/cs20180060","type":"journal-article","created":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T11:45:30Z","timestamp":1529927130000},"page":"1779-1796","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Adenylyl cyclase 6 is required for maintaining acid\u2013base homeostasis"],"prefix":"10.1042","volume":"132","author":[{"given":"S\u00f8ren\u00a0Brandt","family":"Poulsen","sequence":"first","affiliation":[{"name":"InterPrET Center, Department of Biomedicine, Aarhus University, Aarhus DK 8000, Denmark"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caralina","family":"Marin De Evsikova","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish\u00a0Kumar","family":"Murali","sequence":"additional","affiliation":[{"name":"InterPrET Center, Department of Biomedicine, Aarhus University, Aarhus DK 8000, Denmark"},{"name":"Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeppe","family":"Praetorius","sequence":"additional","affiliation":[{"name":"InterPrET Center, Department of Biomedicine, Aarhus University, Aarhus DK 8000, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijuang","family":"Chern","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u00a0A.","family":"Fenton","sequence":"additional","affiliation":[{"name":"InterPrET Center, Department of Biomedicine, Aarhus University, Aarhus DK 8000, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Rieg","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,8,30]]},"reference":[{"key":"2021113010550740600_B1","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1002\/cphy.c140021","article-title":"Molecular mechanisms and regulation of urinary acidification","volume":"4","author":"Kurtz","year":"2014","journal-title":"Compr. 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