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Inhibition of sAC decreased the setpoint for RBC pH<jats:sub>i<\/jats:sub> regulation by ~0.25 pH units compared to controls, and slowed the rates of RBC pH<jats:sub>i<\/jats:sub> recovery after an acid\u2010base disturbance. RBC pH<jats:sub>i<\/jats:sub> recovery was entirely through the anion exchanger (AE) that was in part regulated by HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2010dependent sAC signaling. Inhibition of sAC decreased Hb\u2010O<jats:sub>2<\/jats:sub> affinity during a respiratory acidosis compared to controls and reduced the cooperativity of O<jats:sub>2<\/jats:sub> binding. During in\u00a0vitro simulations of arterial\u2010venous transit, sAC inhibition decreased the amount of O<jats:sub>2<\/jats:sub> that is unloaded by ~11%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>sAC represents a novel acid\u2010base sensor in the RBCs of rainbow trout, where it participates in the modulation of RBC pH<jats:sub>i<\/jats:sub> and blood O<jats:sub>2<\/jats:sub> transport though the regulation of AE activity. If substantiated in other species, these findings may have broad implications for our understanding of cardiovascular physiology in vertebrates.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14205","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T12:20:09Z","timestamp":1721391609000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Soluble adenylyl cyclase is an acid\u2010base sensor in rainbow trout red blood cells that regulates intracellular pH and haemoglobin\u2013oxygen binding"],"prefix":"10.1111","volume":"240","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 California 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