Colonic H(+)-K(+)-ATPase in K(+) conservation and electrogenic Na(+) absorption during Na(+) restriction.
Upregulation of the colonic H(+)-K(+)- ATPase (cHKA) during hyperaldosteronism suggests that it functions in both K(+) conservation and electrogenic Na(+) absorption in the colon when Na(+)-conserving mechanisms are activated. To test this hypothesis, wild-type (cHKA(+/+)) and cHKA-deficient (cHKA(-/-)) mice were fed Na(+)-replete and Na(+)-restricted diets and their responses were analyzed. In both genotypes, Na(+) restriction led to reduced plasma Na(+) and increased serum aldosterone, and mRNAs for the epithelial Na(+) channel (ENaC) beta- and gamma-subunits, channel-inducing factor, and cHKA were increased in distal colon. Relative to wild-type controls, cHKA(-/-) mice on a Na(+)-replete diet had elevated fecal K(+) excretion. Dietary Na(+) restriction led to increased K(+) excretion in knockout but not in wild-type mice. The amiloride-sensitive, ENaC-mediated short-circuit current in distal colon was significantly reduced in knockout mice maintained on either the Na(+)-replete or Na(+)-restricted diet. These results demonstrate that cHKA plays an important role in K(+) conservation during dietary Na(+) restriction and suggest that cHKA-mediated K(+) recycling across the apical membrane is required for maximum electrogenic Na(+) absorption.
Spicer
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Department of Molecular Genetics, Biochemistry and Microbiology, The University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524, USA.
Clarke
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Gawenis
L R
LR
Shull
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GE
D000450:Aldosterone / Q000097:blood; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D003106:Colon / Q000201:enzymology*; D004039:Diet, Sodium-Restricted; D004553:Electric Conductivity; D004848:Epithelium / Q000737:chemistry / Q000502:physiology; D005243:Feces / Q000737:chemistry; D005838:Genotype; D017506:H(+)-K(+)-Exchanging ATPase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007408:Intestinal Absorption; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D015222:Sodium Channels / Q000235:genetics
D012333:RNA, Messenger; D015222:Sodium Channels; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium