{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:10:40Z","timestamp":1778274640004,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T00:00:00Z","timestamp":1435190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["DE 231\/24-2"],"award-info":[{"award-number":["DE 231\/24-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,8,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The regulation of H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> from cytosolic alkalosis has generally been attributed to the activity of Cl<jats:sup>\u2013<\/jats:sup>\u2010coupled acid loaders\/base extruders in most cell types, including brain cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present study demonstrates that outwardly\u2010directed sodium bicarbonate cotransport via electrogenic sodium bicarbonate cotransporter\u00a01 (NBCe1) mediates the major fraction of H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> regulation from cytosolic alkalosis in mouse cortical astrocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cl<jats:sup>\u2013<\/jats:sup>\u2010coupled acid\u2010loading transporters play only a minor role in the regulation of H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> from alkalosis in mouse cortical astrocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NBCe1\u2010mediated H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> regulation from alkalosis was dominant, with the support of intracellular carbonic anhydrase\u00a0II, even when the intra\u2010 and extracellular [HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup>] was very low (&lt;1mM), as in nominally CO<jats:sub>2<\/jats:sub>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup> free condition.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A reversed NBCe1 in astrocytes may also be significant for stabilizing extracellular pH in brain tissue.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Recovery of intracellular pH from cytosolic alkalosis has been attributed primarily to Cl<jats:sup>\u2013<\/jats:sup> coupled acid loaders\/base extruders such as Cl<jats:sup>\u2013<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup> or Cl<jats:sup>\u2013<\/jats:sup>\/OH<jats:sup>\u2013<\/jats:sup> exchangers. We have studied this process in cortical astrocytes from wild\u2010type and transgenic mouse models with gene deletion for the electrogenic sodium bicarbonate cotransporter\u00a01 (NBCe1) and for carbonic anhydrase (CA) isoform II. An acute cytosolic alkalosis was induced by the removal of either CO<jats:sub>2<\/jats:sub>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup> or butyric acid, and the subsequent acid loading was analysed by monitoring changes in cytosolic H<jats:sup>+<\/jats:sup> or Na<jats:sup>+<\/jats:sup> using ion\u2010sensitive fluorescent dyes. We have identified that NBCe1 reverses during alkalosis and contributes more than 70% to the rate of recovery from alkalosis by extruding Na<jats:sup>+<\/jats:sup> and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup>. After CA inhibition or in CAII\u2010knockout (KO) cells, the rate of recovery was reduced by 40%, and even by 70% in the nominal absence of CO<jats:sub>2<\/jats:sub>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup>. Increasing the extracellular K<jats:sup>+<\/jats:sup> concentration modulated the rate of acid loading in wild\u2010type cells, but not in NBCe1\u2010KO cells. Removing chloride had only a minor effect on the recovery from alkalosis. Reversal of NBCe1 by reducing pH\/[HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup>] was demonstrated in astrocytes and in <jats:italic>Xenopus<\/jats:italic> oocytes, in which human NBCe1 was heterologously expressed. The results obtained suggest that reversed NBCe1, supported by CAII activity, plays a major role in acid\u2010loading cortical astrocytes to support recovery from cytosolic alkalosis.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270086","type":"journal-article","created":{"date-parts":[[2015,5,20]],"date-time":"2015-05-20T10:08:45Z","timestamp":1432116525000},"page":"3533-3547","source":"Crossref","is-referenced-by-count":45,"title":["Reversed electrogenic sodium bicarbonate cotransporter\u00a01 is the major acid loader during recovery from cytosolic alkalosis in mouse cortical astrocytes"],"prefix":"10.1113","volume":"593","author":[{"given":"Shefeeq M.","family":"Theparambil","sequence":"first","affiliation":[{"name":"Department of General Zoology, Faculty of Biology University of Kaiserslautern  Kaiserslautern Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zinnia","family":"Naoshin","sequence":"additional","affiliation":[{"name":"Department of General Zoology, 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