Nongastric H,K-ATPase: Structure and Functional Properties

Nongastric H,K-ATPases whose catalytic subunits (AL1) encoded by human ATP1AL1 and homologous animal genes comprise the third distinct group within the X,K-ATPase family. No unique nongastric ? has been identified. Precise in situcolocalization and strong association of AL1 with ?1 of Na,K-ATPase was detected in apical membranes of rodent prostate epithelium. In this tissue, ?1NK serves as an authentic subunit of both the Na,K- and nongastric H,K-pumps. Upon expression in Xenopusoocytes the human AL1 can assemble with ?1NK, and more efficiently with gastric ?HK, into functional H,K-pumps. Both AL1? complexes exhibit a similar K-affinity, and their K-transport depends on intra- and extracellular Na. These data provide new evidence that nongastric H,K-ATPase can perform NaK-exchange, and indicate that ? does not significantly affect this ion-pump function. Analysis of human nongastric H,K-ATPase expressed in Sf-21 insect cells revealed that AL1?HK exhibits substantial enzymatic activities in K-free medium and K stimulates, but Na has inhibitory effect on ATP hydrolysis. Thus, although the nongastric H,K-ATPase can function as NaK exchanger, its reaction mechanism is different from that of the Na,K-ATPase. Human nongastric H,K-ATPase is highly sensitive to bufalin, digoxin, and digitoxin, but almost resistant to digoxigenin and ouabagenin.