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Soluble adenylyl cyclase (sAC) is a source of the second messenger cyclic adenosine 3′, 5′ monophosphate (cAMP). sAC is directly regulated by bicarbonate (HCO −  3 ) ions. In living cells, HCO −  3  ions are in nearly instantaneous equilibrium with carbon dioxide (CO 2 ) and pH due to the ubiquitous presence of carbonic anhydrases. Numerous biological processes are regulated by CO 2 , HCO −  3 , and/or pH, and in a number of these, sAC has been shown to function as a physiological CO 2 /HCO 3 /pH sensor. In this review, we detail the known pH sensing functions of sAC, and we discuss two highly-studied, pH-dependent pathways in which sAC might play a role.

pH sensing via bicarbonate-regulated “soluble” adenylyl cyclase (sAC)