Fig. 4.

Sensing and regulation of systemic pH and acid/base status by carbonic anhydrase (CA), sAC, and vacuolar proton pump (VHA). Alkalosis due to elevated extracellular HCO₃⁻ and/or pH results in elevated extracellular CO₂, a reaction catalyzed by extracellular CA_IV. CO₂ diffuses inside the cell, where it is hydrated into H⁺ and HCO₃⁻. sAC is activated by intracellular HCO₃⁻ to produce cAMP, which promotes (via PKA) the insertion of VHA-containing vesicles into the cell membrane facing the alkalosis. Membrane-inserted VHAs secrete H⁺, which counteract the alkalosis. sAC may also modulate the activity of HCO₃⁻ transporters in the opposite membrane. In the clear cells of the epididymis and in A-type renal intercalated cells, Side A is the apical (mucosal) side and Side B is the basolateral (serosal) side. The polarity is reversed in base-secreting cells of the shark gill and in B-type renal intercalated cells