Human ATP1AL1 gene encodes a ouabain-sensitive H-K-ATPase.
The cDNA for ATP1AL1, the fifth member of the human Na-K-adenosinetriphosphatase (ATPase)/H-K-ATPase gene family, was recently cloned (A. V. Grishin, V. E. Sverdlov, M. B. Kostina, and N. N. Modyanov. FEBS Lett. 349: 144-150, 1994). The encoded protein (ATP1AL1) has all the primary structural features common to the catalytic alpha-subunit of ion-transporting P-type ATPases and is similar (63-64% identity) to the Na-K-ATPase alpha-subunit isoforms and the gastric H-K-ATPase alpha-subunit. In this study, ATP1AL1 was expressed in Xenopus laevis oocytes in combination with the beta-subunit of rabbit gastric H-K-ATPase. The functional properties of the stable alpha/beta-complex were studied by 86Rb+ uptake and demonstrated that ATP1AL1 is a novel human K(+)-dependent ATPase [apparent half-constant activation/(K1/2) for K+ approximately 375 microM)]. ATP1AL1-mediated inward K+ transport was inhibited by ouabain (inhibition constant approximately 13 microM) and was found to be inhibited by high concentrations of SCH-28080 (approximately 70% at 500 microM). ATP1AL1 expression resulted in the alkalinization of the oocytes' cytoplasm and ouabain-sensitive proton extrusion, as measured with pH-sensitive microelectrodes. These data argue that ATP1AL1 is the catalytic alpha-subunit of a human nongastric P-type ATPase capable of exchanging extracellular potassium for intracellular protons.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005796:Genes; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D010042:Ouabain / Q000493:pharmacokinetics*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D014982:Xenopus laevis
D007093:Imidazoles; C035235:Sch 28080; D010042:Ouabain; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium