Ion Channels – Membrane Transport – Integrative Physiology

Kidney International (1998) 54, 1233–1239; doi:10.1046/j.1523-1755.1998.00105.x

Colonic H+-K+-ATPase is induced and mediates increased HCO3- reabsorption in inner medullary collecting duct in potassium depletion

Suguru Nakamura, Hassane Amlal, John H Galla and Manoocher Soleimani

Department of Medicine, University of Cincinnati School of Medicine, and Veterans Affairs Medical Center, Cincinnati, Ohio, USA

Correspondence: Manoocher Soleimani, M.D., Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati, 231 Bethesda Avenue, MSB 5502, Cincinnati, Ohio 45267-0585, USA. E-mail: Manoocher.soleimani@uc.edu

Received 9 February 1998; Revised 28 April 1998; Accepted 14 May 1998.

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Abstract

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 muM 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 muM 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.

Keywords:

acid-base transporters, H-K-ATPase, bicarbonate reabsorption, kidney, IMCD, collecting duct, mtetabolic acidosis

Abbreviations:

CD, collecting duct; CCD, cortical collecting duct; cHKA, colonic H-K-ATPase; gHKA, gastric H-K-ATPase; HKA, H-K-ATPase; IMCD, inner medullary collecting duct; JtCO2, net HCO3- flux; OMCD, outer medullary collecting duct; SCH, Schering 28080

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