Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase

Soluble adenylyl cyclase (sAC; ADCY10) is a bicarbonate (HCO₃ ^-)-regulated enzyme responsible for the generation of cyclic adenosine monophosphate (cAMP). sAC is distributed throughout the cell and within organelles and, as such, plays a role in numerous cellular signalling pathways. Carbonic anhydrases (CAs) nearly instantaneously equilibrate HCO₃ ^-, protons and carbon dioxide (CO₂); because of the ubiquitous presence of CAs within cells, HCO₃ ^--regulated sAC can respond to changes in any of these factors. Thus, sAC can function as a physiological HCO₃ ^-/CO₂/pH sensor. Here, we outline examples where we have shown that sAC responds to changes in HCO₃ ^-, CO₂ or pH to regulate diverse physiological functions.