APStracts 2:0180C, 1995.

The human atp1al1 gene encodes a ouabain-sensitive h,k-atpase. Modyanov, Nikolai N., Paul M. Mathews, Alexander V. Grishin, Pascal Beguin, Ahmed T. Beggah, Bernard C. Rossier, Jean-Daniel Horisberger, and K[umlaut]athi Geering. Institute of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland; Department of Pharmacology, Medical College of Ohio, Toledo, OH, 43699-0008; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871, Russia; and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510.

APStracts 2:0180C, 1995.

The cDNA for ATP1AL1--the fifth member of the human Na,K-ATPase/H,K -ATPase gene family--was recently cloned (Grishin, A.V., Sverdlov, V.E., Kostina, M.B. and Modyanov, N.N. (1994) FEBS Lett., 349, 144 -150). The encoded protein (ATP1AL1) has all the primary structural features common to the catalytic [alpha]-subunit of ion-transporting P-type ATPases, and is equally 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 K1/2 for K+ 375 [mu]M). ATP1AL1 mediated inward K+-transport was inhibited by ouabain (Ki 13 [mu]M) and was found to be inhibited by high concentrations of SCH 28080 ( 70% at 500 [mu]M). ATP1AL1 expression resulted in the alkalinization of the oocytes' cytoplasm and ouabain -sensitive proton extrusion as measured with pH-sensitive micro -electrodes. These data argue that ATP1AL1 is the catalytic [alpha] -subunit of a human, non-gastric P-type ATPase capable of exchanging extracellular potassium for intracellular protons.

Received 17 February 1995; accepted in final form 26 April 1995.
APS Manuscript Number C93-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  9 May 1995.