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AJP - Renal Physiology, Vol 270, Issue 3 432-F439, Copyright © 1996 by American Physiological Society
ARTICLES |
S. M. Wall
Division of Nephrology, University of Texas Medical School at Houston 77030, USA.
We have shown that NH4+ and K+ compete for extracellular binding on the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the rat terminal inner medullary collecting duct (tIMCD). The present study explored whether the Na(+)-K(+)-ATPase modulates transepithelial net acid flux [JH+ = total CO2 absorption (JtCO2) + total ammonia secretion (JtAM)]. Tubules from the tIMCD were dissected from deoxycorticosterone (DOC)-treated rats and perfused in vitro. Perfusate and bath were identical physiological saline solutions containing 25 mM NaHCO3 + 6 mM NH4Cl or were NH4Cl or were NH4Cl free. With NH4+ present, the fall in total CO2 from perfusate to collected fluid (delta tCO2, 2.5 +/- 0.4 mM; n = 6) was accompanied by an increase in collected total ammonia concentration (0.2 +/- 0.1 mM). However, in the absence of NH4Cl, delta tCO2 was only 0.9 +/- 0.2 mM (P < 0.05, n = 5). To determine the mechanism of this NH4Cl-induced increase in net acid secretion, the effect of Na+ pump inhibition on net acid secretion was explored. With NH4Cl present, JCO2 was 3.8 +/- 0.5 pmol.mm-1.min-1 (ouabain absent) but declined to 1.6 +/- 0.3 pmol.mm-1.min-1 with ouabain addition to the bath (n = 7, P < 0.05). Furthermore, in the presence of NH4Cl, intracellular pH (pHi) increased from 7.05 +/- 0.02 to 7.15 +/- 0.02 (P < 0.05, n = 5) with ouabain addition and returned to 7.06 +/- 0.03 (P < 0.05) with ouabain removal. However, in the absence of NH4Cl, ouabain failed to reduce JtCO2 (P = NS, n = 5), and an increase in pHi was not observed (n = 4, P = NS). In conclusion, NH4+ augments net acid secretion likely by serving as a proton source for bicarbonate absorption and titration of other luminal buffers. This ammonium pathway is dependent on the basolateral membrane Na(+)-K(+)-ATPase.
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S. M. Wall, B. S. Davis, K. A. Hassell, P. Mehta, and S. J. Park In rat tIMCD, NH+4 uptake by Na+-K+-ATPase is critical to net acid secretion during chronic hypokalemia Am J Physiol Renal Physiol, December 1, 1999; 277(6): F866 - F874. [Abstract] [Full Text] [PDF]
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S. M. Wall, P. Mehta, and T. D. DuBose Jr. Dietary K+ restriction upregulates total and Sch-28080-sensitive bicarbonate absorption in rat tIMCD Am J Physiol Renal Physiol, October 1, 1998; 275(4): F543 - F549. [Abstract] [Full Text] [PDF]
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S. M. Wall Ouabain reduces net acid secretion and increases pHi by inhibiting NH+4 uptake on rat tIMCD Na+-K+-ATPase Am J Physiol Renal Physiol, December 1, 1997; 273(6): F857 - F868. [Abstract] [Full Text] [PDF]
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