Reduction in sensitivity to Cl- channel blockers by HCO3- -CO2 in rabbit cortical collecting duct.
We examined the ability of HCO3- -CO2 to modify the potency of Cl- channel blockers in the renal cortical collecting duct (CCD) for the following two reasons. 1) From a practical point of view, there is, to our knowledge, no information regarding the effect of the HCO3- -CO2 buffer system on the potency of Cl- channel blockers. 2) We showed in the companion manuscript [Am. J. Physiol. 257 (Cell Physiol. 26): C94-C101, 1989] that HCO3- -CO2 stimulates transepithelial anion exchange in the CCD. Based on precedent in the literature, we postulated that HCO3- stimulates the basolateral membrane Cl- conductance. Here, we demonstrate that several Cl- channel blockers can reduce CCD Cl- self exchange when the solutions are buffered in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Concentrations of blockers producing 80% inhibition in HEPES, pH 7.4, produced only 20% inhibition in 25 mM HCO3- -CO2, pH 7.4. The ability of HCO3- -CO2 to reduce blocker potency had an IC50 of only 2 mM. We also examined interactions of HCO3- -CO2 and blockers with regard to the principal cell basolateral Cl- conductance. Blockers did not alter the Rb+ flux, a marker of K+ transport, but did reduce transepithelial conductance (GT), i.e., the blockers inhibited the principal cell basolateral Cl- conductance. As was the case with intercalated cell anion exchange, GT measurements indicated that HCO3- -CO2 impaired the ability of Cl- channel blockers to inhibit the principal cell Cl- conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsuzaki
K
K
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Schuster
V L
VL
Stokes
J B
JB
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000838:Anions; D001639:Bicarbonates / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology*; D018118:Chloride Channels; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004553:Electric Conductivity; D005942:Gluconates / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels; D058610:Isobutyrates; D007684:Kidney Tubules / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009550:Nigericin / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011817:Rabbits; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000838:Anions; D001639:Bicarbonates; D002087:Butyrates; D018118:Chloride Channels; D002712:Chlorides; D005942:Gluconates; D007473:Ion Channels; D058610:Isobutyrates; D008565:Membrane Proteins; D009579:Nitrobenzoates; D015221:Potassium Channels; D062367:ortho-Aminobenzoates; D002245:Carbon Dioxide; C059537:3',5-dichlorodiphenylamine-2-carboxylic acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000584:Amiloride; C020380:isobutyric acid; C001209:fenamic acid; D004159:Diphenylamine; C030691:gluconic acid; D009550:Nigericin; D011188:Potassium