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

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.