|Title||Soluble adenylyl cyclase is an acid-base sensor in epithelial base-secreting cells|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Roa J.N, Tresguerres M|
|Journal||Am J Physiol Cell PhysiolAm J Physiol Cell Physiol|
|ISBN Number||1522-1563 (Electronic)<br/>0363-6143 (Linking)|
Blood acid-base regulation by specialized epithelia, such as gills and kidney, requires the ability to sense blood acid-base status. Here, we developed primary cultures of ray (Urolophus halleri) gill cells to study mechanisms for acid-base sensing without the interference of whole animal hormonal regulation. Ray gills have abundant base-secreting cells, identified by their noticeable expression of vacuolar-type H(+)-ATPase (VHA), and also express the evolutionarily conserved acid-base sensor soluble adenylyl cyclase (sAC). Exposure of cultured cells to extracellular alkalosis (pH 8.0, 40 mM HCO3 (-)) triggered VHA translocation to the cell membrane, similar to previous reports in live animals experiencing blood alkalosis. VHA translocation was dependent on sAC, as it was blocked by the sAC-specific inhibitor KH7. Ray gill base-secreting cells also express transmembrane adenylyl cyclases (tmACs); however, tmAC inhibition by 2',5'-dideoxyadenosine did not prevent alkalosis-dependent VHA translocation, and tmAC activation by forskolin reduced the abundance of VHA at the cell membrane. This study demonstrates that sAC is a necessary and sufficient sensor of extracellular alkalosis in ray gill base-secreting cells. In addition, this study indicates that different sources of cAMP differentially modulate cell biology.
|Short Title||American journal of physiology. Cell physiologyAmerican journal of physiology. Cell physiology|
|Alternate Journal||American journal of physiology. Cell physiology|
In summary, this study established sAC as a sensor of alkalosis in ray gill base-secreting cells. Because sAC, the cAMP pathway, and VHA are widespread in eukaryotic cells, this could be an evolutionarily conserved mechanism for sensing and counteracting alkalosis.