Colonic H+-K+-ATPase is induced and mediates increased HCO3- reabsorption in inner medullary collecting duct in potassium depletion.
BACKGROUND
Potassium depletion increases HCO3- reabsorption in outer medullary collecting duct (OMCD) by activation of colonic (c) H-K-ATPase (HKA). The purpose of the current experiments was to examine the role of the isoforms of HKA in HCO3- reabsorption by terminal inner medullary collecting duct (IMCD) cells in potassium depletion.


METHODS
Sprague-Dawley rats were fed a potassium-free diet and studied after 8 to 10 days. mRNA expression of HKA isoforms in terminal portion of inner medulla was examined and correlated with HCO3- reabsorption in the terminal IMCD.


RESULTS
Gastric (g) HKA mRNA decreased whereas colonic (c) HKA mRNA expression was heavily induced in terminal portion of inner medulla in potassium depleted rats. Net HCO3- flux (JtCO2) in terminal IMCD increased in potassium depletion (4.56 to 7.06 pmol/min/mm tubule length, P < 0.001). In normal rats, 1 mM ouabain in perfusate had no effect on JtCO2, whereas 10 microM Schering 28080 (SCH) decreased JtCO2 to 2.4 (P < 0.002). In KD rats, 1 mM ouabain decreased JtCO2 to 4.9 (P < 0.005) and 10 microM SCH decreased JtCO2 to 3.3 (P < 0.001). However, the inhibitory effects of SCH and ouabain on JtCO2 in potassium depleted animals were not additive.


CONCLUSIONS
The data indicate that gHKA is suppressed whereas cHKA is induced in potassium depletion and mediates increased HCO3- reabsorption in terminal IMCD. The results further indicate that cHKA in vivo is sensitive to both SCH and ouabain.
Department of Medicine, University of Cincinnati School of Medicine, and Veterans Affairs Medical Center, Ohio, USA.
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Nakamura
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Amlal
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JH
Galla
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M
Soleimani
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D003106:Colon / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D017506:H(+)-K(+)-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics; D007008:Hypokalemia / Q000235:genetics / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism*; D017419:Potassium, Dietary / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000201:enzymology
D001639:Bicarbonates; D007093:Imidazoles; D007527:Isoenzymes; D017419:Potassium, Dietary; D012333:RNA, Messenger; C035235:Sch 28080; D010042:Ouabain; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium