To investigate whether nongastric H+-K+-ATPases transport Na+in exchange for K+and whether different β-isoforms influence their transport properties, we compared the functional properties of the catalytic subunit of human nongastric H+-K+-ATPase, ATP1al1 (AL1), and of the Na+-K+-ATPase α1-subunit (α1) expressed in Xenopus oocytes, with different β-subunits. Our results show that βHK and β1-NK can produce functional AL1/β complexes at the oocyte cell surface that, in contrast to α1/β1NK and α1/βHK complexes, exhibit a similar apparent K+affinity. Similar to Na+-K+-ATPase, AL1/β complexes are able to decrease intracellular Na+concentrations in Na+-loaded oocytes, and their K+transport depends on intra- and extracellular Na+concentrations. Finally, controlled trypsinolysis reveals that β-isoforms influence the protease sensitivity of AL1 and α1and that AL1/β complexes, similar to the Na+-K+-ATPase, can undergo distinct K+-Na+- and ouabain-dependent conformational changes. These results provide new evidence that the human nongastric H+-K+-ATPase interacts with and transports Na+in exchange for K+and that β-isoforms have a distinct effect on the overall structural integrity of AL1 but influence its transport properties less than those of the Na+-K+-ATPase α-subunit.
