Coordination between glycogen metabolism and pH regulation in stingray gill cells

Elasmobranchs (shark, rays and relatives) have specialized epithelial cells in their gills that maintain blood pH homeostasis that are functionally analogous to distal tubule cells in the mammalian kidney. The gill cells are either enriched with the Na⁺/K⁺-ATPase (NKA) and responsible for acid secretion or enriched for the vacuolar-type V-H⁺-ATPase (VHA) and responsible for base secretion; both cell types are enriched in mitochondria and glycogen stores that support their high metabolic rates. In this study, we isolated and cultured stingray gill cells and found that the subcellular localization of glycogen coincides with that of NKA and VHA. Under control conditions, glycogen and NKA were located at the cell membrane of acid-secreting cells while glycogen and VHA were in the cytoplasm of the base-secreting cells. During an alkalosis, NKA and glycogen localization in the acid-secreting cells remained unchanged; however, both VHA and glycogen localized to the cell membrane of base-secreting cells. Interestingly, this process was prevented by pharmacological inhibition of the acid-base sensing enzyme, soluble adenylyl cyclase (sAC). This suggests a novel mechanism coupling glycogen metabolism with acid-base regulation that sustains ATPase function during sudden periods of increased energy demand. Since VHA, sAC, and glycogen are evolutionarily widespread, this mechanism may apply broadly to other organisms and systems including mammalian kidney cells.