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We tested the prevailing hypothesis that paCA would interfere with red blood cell (RBC) intracellular pH regulation by \u03b2-adrenergic sodium-proton exchangers (\u03b2-NHE) that protect pH-sensitive haemoglobin\u2013oxygen (Hb\u2013O2) binding during an acidosis. In an open system that mimics the gills, \u03b2-NHE activity increased Hb\u2013O2 saturation during a respiratory acidosis in the presence or absence of paCA, whereas the effect was abolished by NHE inhibition. However, in a closed system that mimics the tissue capillaries, paCA disrupted the protective effects of \u03b2-NHE activity on Hb\u2013O2 binding. The gills are an open system, where CO2 generated by paCA can diffuse out and is not available to acidifying the RBCs. Therefore, branchial paCA in teleosts may not interfere with RBC pH regulation by \u03b2-NHEs, and other explanations for the evolutionary loss of the enzyme must be considered.<\/jats:p>","DOI":"10.1242\/jeb.246016","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T08:34:42Z","timestamp":1694421282000},"source":"Crossref","is-referenced-by-count":8,"title":["A novel perspective on the evolutionary loss of plasma-accessible carbonic anhydrase at the teleost gill"],"prefix":"10.1242","volume":"226","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1712-1370","authenticated-orcid":false,"given":"Till S.","family":"Harter","sequence":"first","affiliation":[{"name":"Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego , La Jolla, CA 92093 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6948-981X","authenticated-orcid":false,"given":"Emma A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego , La Jolla, CA 92093 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7090-9266","authenticated-orcid":false,"given":"Martin","family":"Tresguerres","sequence":"additional","affiliation":[{"name":"Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego , La Jolla, CA 92093 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"2023101109051183000_JEB246016C1","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1126\/science.1107793","article-title":"Evolution of oxygen secretion in fishes and the emergence of a complex physiological system","volume":"307","author":"Berenbrink","year":"2005","journal-title":"Science"},{"key":"2023101109051183000_JEB246016C2","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/j.1748-1716.2010.02243.x","article-title":"Magnitude of the Root effect in red blood cells and haemoglobin solutions of fishes: a tribute to August Krogh","volume":"202","author":"Berenbrink","year":"2011","journal-title":"Acta Physiol."},{"key":"2023101109051183000_JEB246016C3","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1111\/j.1748-1716.1904.tb01382.x","article-title":"\u00dcber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlens\u00e4urespannung des blutes auf dessen Sauerstoffbindung \u00fcbt","volume":"16","author":"Bohr","year":"1904","journal-title":"Skand. 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