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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Loss of acidification of anterior prostate fluids in Atp12a-null mutant mice indicates that nongastric H-K-ATPase functions as proton pump in vivo

¹Department of Physiology, Pharmacology, Metabolism, and Cardiovascular Sciences, Medical University of Ohio, Toledo, Ohio; ²Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; and ³Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio

Submitted 31 January 2006 ; accepted in final form 23 February 2006

The physiological functions of nongastric (colonic) H-K-ATPase (gene symbol Atp12a), unlike those of Na-K-ATPase and gastric H-K-ATPase, are poorly understood. It has been suggested that it pumps Na⁺ more efficiently than H⁺; however, so far, there is no direct evidence that it pumps H⁺ in vivo. Previously, we found that the nongastric H-K-ATPase -subunit is expressed in apical membranes of rodent anterior prostate epithelium, in a complex with the Na-K-ATPase ₁-subunit. Here we report the effects of Atp12a gene ablation on polarization of the ₁-subunit and secretory function of the anterior prostate. In nongastric H-K-ATPase-deficient prostate, the Na-K-ATPase -subunit resided exclusively in basolateral membranes; however, the ₁-subunit disappeared from apical membranes, demonstrating that ₁ is an authentic subunit of nongastric H-K-ATPase in vivo and that apical localization of ₁ in the prostate is completely dependent on its association with the nongastric H-K-ATPase -subunit. A remarkable reduction in acidification of anterior prostate fluids was observed: pH 6.38 ± 0.14 for wild-type mice and 6.96 ± 0.10 for homozygous mutants. These results show that nongastric H-K-ATPase is required for acidification of luminal prostate fluids, thereby providing a strong in vivo correlate of previous functional expression studies demonstrating that it operates as a proton pump.

hydrogen-potassium-adenosinetriphosphatase; male accessory glands; proton transport; sorting

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