Bicarbonate‐Stimulated Soluble Adenylyl Cyclase Is an Acid‐Base Sensor Present in the Cell Cytoplasm and Nucleus of Elasmobranch Fishes

Regulation of acid‐base stress (i.e. carbon dioxide [CO 2 ], pH, and bicarbonate [HCO 3 − ]) is essential for proper functioning of cells, organs, and whole‐animals; however, the mechanisms for sensing acid‐base stress are largely unknown in marine animals. One such sensing mechanism involves the evolutionarily conserved acid‐base sensor soluble adenylyl cyclase (sAC, adcy10), which is present and co‐expressed along with transmembrane adenylyl cyclases (tmACs, adcy1–9) in leopard shark and round ray acid‐base regulatory gill cells. Both sAC and tmACs produce the second messenger cyclic adenosine monophosphate (cAMP), but have different regulatory effects depending on species and tissue type. In isolated base‐secreting cells exposed to alkalosis, HCO 3 − activation of sAC led to translocation of the proton pump to the cell membrane, whereas forskolin activation of tmACs did not. Additionally, sAC is present in other shark tissues including the rectal gland, cornea, intestine, and white muscle where it likely regulates acid‐base status in response to tissue‐specific physiological acid‐base disturbances. Furthermore, sAC is present in the cell nucleus where it likely facilitates regulation of gene expression through protein kinase A (PKA) phosphorylation of target proteins. Support or Funding Information JNR is supported by the William Townsend Porter Pre‐doctoral Fellowship from the American Physiological Society. This research was supported by NIH Training Grant in Marine Biotechnology (GM067550) to JNR and NSF grant IOS 1354181 to MT