Luminal acidification in K-replete OMCDi: inhibition of bicarbonate absorption by K removal and luminal Ba

Abstract

We have previously demonstrated that significant luminal acidification in the K-replete rabbit inner stripe of the outer medullary collecting duct (OMCDi) occurs via a renal H-K-adenosinetriphosphatase (H-K-ATPase) sensitive to several of the gastric H-K-ATPase inhibitors. To investigate further the mechanism of K-dependent luminal acidification in K-replete OMCDi, we examined the effects of luminal K removal, luminal addition of Ba in the presence and absence of luminal 5.0 nM bafilomycin A1 (BAF), and basolateral addition of Ba on net bicarbonate flux (JtCO2, pmol.mm-1.min-1) and transepithelial voltage (VT, mV). Removal of K from the perfusate inhibited JtCO2 by 74% (13.4 +/- 4.0 for control, 3.5 +/- 1.4 pmol.mm-1.min-1 for experimental, P < 0.05) and was statistically equivalent to the degree of inhibition previously observed under identical experimental conditions by either 10 microM Sch-28080 or 10 microM A-80915A. Approximately 50% inhibition of JtCO2 was observed following luminal application of 2.0 mM Ba2+, and the degree of inhibition was statistically equivalent regardless of whether BAF was present (12.2 +/- 2.7 for control, 6.0 +/- 1.4 pmol.mm-1.min-1 for 2.0 mM Ba2+, P < 0.05; 9.6 +/- 1.2 for control with 5 nM BAF, 5.7 +/- 1.3 pmol.mm-1.min-1 for 2.0 mM Ba2+ with 5 nM BAF, P < 0.05). Additionally, increasing the luminal concentration of Ba2+ from 2.0 to 4.0 mM resulted in no further inhibition of JtCO2 (8.5 +/- 1.7 for control, 3.9 +/- 1.3 pmol.mm-1.min-1 for 4.0 mM Ba2+, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)