ENaC inhibition stimulates HCl secretion in the mouse cortical collecting duct. II. Bafilomycin-sensitive H+ secretion

Author:

Nanami Masayoshi1,Pech Vladimir1,Lazo-Fernandez Yoskaly1,Weinstein Alan M.23,Wall Susan M.14

Affiliation:

1. Department of Medicine. Emory University School of Medicine, Atlanta, Georgia;

2. Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York; and

3. Department of Medicine, Weill Medical College of Cornell University, New York, New York

4. Department of Physiology, Emory University School of Medicine, Atlanta, Georgia;

Abstract

Epithelial Na+ channel (ENaC) blockade stimulates stilbene-sensitive conductive Cl secretion in the mouse cortical collecting duct (CCD). This study's purpose was to determine the co-ion that accompanies benzamil- and DIDS-sensitive Cl flux. Thus transepithelial voltage, VT, as well as total CO2 (tCO2) and Cl flux were measured in CCDs from aldosterone-treated mice consuming a NaCl-replete diet. We reasoned that if stilbene inhibitors (DIDS) reduce conductive anion secretion they should reduce the lumen-negative VT. However, during ENaC blockade (benzamil, 3 μM), DIDS (100 μM) application to the perfusate reduced net H+ secretion, which increased the lumen-negative VT. Conversely, ENaC blockade alone stimulated H+ secretion, which reduced the lumen-negative VT. Application of an ENaC inhibitor to the perfusate reduced the lumen-negative VT, increased intercalated cell intracellular pH, and reduced net tCO2 secretion. However, benzamil did not change tCO2 flux during apical H+-ATPase blockade (bafilomycin, 5 nM). The increment in H+ secretion observed with benzamil application contributes to the fall in VT observed with application of this diuretic. As such, ENaC blockade reduces the lumen-negative VT by inhibiting conductive Na+ absorption and by stimulating H+ secretion by type A intercalated cells. In conclusion, 1) in CCDs from aldosterone-treated mice, benzamil application stimulates HCl secretion mediated by the apical H+-ATPase and a yet to be identified conductive Cl transport pathway; 2) benzamil-induced HCl secretion is reversed with the application of stilbene inhibitors or H+-ATPase inhibitors to the perfusate; and 3) benzamil reduces VT not only by inhibiting conductive Na+ absorption, but also by stimulating H+ secretion.

Funder

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

American Society of Nephrology (ASN)

Publisher

American Physiological Society

Subject

Physiology

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