{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:24:15Z","timestamp":1792427055640,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,12,20]],"date-time":"2005-12-20T00:00:00Z","timestamp":1135036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p>Plasmalemmal Cl<jats:sup>\u2212<\/jats:sup>\u2013HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchangers regulate intracellular pH and [Cl<jats:sup>\u2212<\/jats:sup>] and cell volume. In polarized epithelial cells, they contribute also to transepithelial secretion and reabsorption of acid\u2013base equivalents and of Cl<jats:sup>\u2212<\/jats:sup>. Members of both the SLC4 and SLC26 mammalian gene families encode Na<jats:sup>+<\/jats:sup>\u2010independent Cl<jats:sup>\u2212<\/jats:sup>\u2013HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchangers. Human SLC4A1\/AE1 mutations cause either the erythroid disorders spherocytic haemolytic anaemia or ovalocytosis, or distal renal tubular acidosis. SLC4A2\/AE2 knockout mice die at weaning. Human SLC4A3\/AE3 polymorphisms have been associated with seizure disorder. Although mammalian SLC4\/AE polypeptides mediate only electroneutral Cl<jats:sup>\u2212<\/jats:sup>\u2013anion exchange, trout erythroid AE1 also promotes osmolyte transport and increased anion conductance. Mouse AE1 is required for DIDS\u2010sensitive erythroid Cl<jats:sup>\u2212<\/jats:sup> conductance, but definitive evidence for mediation of Cl<jats:sup>\u2212<\/jats:sup> conductance is lacking. However, a single missense mutation allows AE1 to mediate both electrogenic SO<jats:sub>4<\/jats:sub><jats:sup>2<\/jats:sup><jats:sup>\u2212<\/jats:sup>\u2013Cl<jats:sup>\u2212<\/jats:sup> exchange or electroneutral, H<jats:sup>+<\/jats:sup>\u2010independent SO<jats:sub>4<\/jats:sub><jats:sup>2<\/jats:sup><jats:sup>\u2212<\/jats:sup>\u2013SO<jats:sub>4<\/jats:sub><jats:sup>2<\/jats:sup><jats:sup>\u2212<\/jats:sup> exchange. In the <jats:italic>Xenopus<\/jats:italic> oocyte, the AE1 C\u2010terminal cytoplasmic tail residues reported to bind carbonic anhydrase II are dispensable for Cl<jats:sup>\u2212<\/jats:sup>\u2013Cl<jats:sup>\u2212<\/jats:sup> exchange, but required for Cl<jats:sup>\u2212<\/jats:sup>\u2013HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchange. AE2 is acutely and independently inhibited by intracellular and extracellular H<jats:sup>+<\/jats:sup>, and this regulation requires integrity of the most highly conserved sequence of the AE2 N\u2010terminal cytoplasmic domain. Individual missense mutations within this and adjacent regions identify additional residues which acid\u2010shift pH<jats:sub>o<\/jats:sub> sensitivity. These regions together are modelled to form contiguous surface patches on the AE2 cytoplasmic domain. In contrast, the N\u2010terminal variant AE2c polypeptide exhibits an alkaline\u2010shifted pH<jats:sub>o<\/jats:sub> sensitivity, as do certain transmembrane domain His mutants. AE2\u2010mediated anion exchange is also stimulated by ammonium and by hypertonicity by a mechanism sensitive to inhibition by chelation of intracellular Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup> and by calmidazolium. This growing body of structure\u2013function data, together with increased structural information, will advance mechanistic understanding of SLC4 anion exchangers.<\/jats:p>","DOI":"10.1113\/expphysiol.2005.031765","type":"journal-article","created":{"date-parts":[[2005,10,26]],"date-time":"2005-10-26T07:13:10Z","timestamp":1130310790000},"page":"153-161","source":"Crossref","is-referenced-by-count":194,"title":["Molecular physiology of SLC4 anion exchangers"],"prefix":"10.1113","volume":"91","author":[{"given":"Seth 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