Reduction in sensitivity to Cl- channel blockers by HCO3- -CO2 in rabbit cortical collecting duct

Am J Physiol. 1989 Jul;257(1 Pt 1):C102-9. doi: 10.1152/ajpcell.1989.257.1.C102.


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)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amiloride / pharmacology
  • Animals
  • Anions
  • Bicarbonates / pharmacology*
  • Butyrates / pharmacology
  • Carbon Dioxide / pharmacology*
  • Chloride Channels
  • Chlorides / antagonists & inhibitors
  • Chlorides / metabolism*
  • Diphenylamine / analogs & derivatives
  • Diphenylamine / pharmacology
  • Drug Interactions
  • Electric Conductivity
  • Gluconates / pharmacology
  • Hydrogen-Ion Concentration
  • Ion Channels
  • Isobutyrates
  • Kidney Tubules / metabolism*
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / metabolism*
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism*
  • Nigericin / pharmacology
  • Nitrobenzoates / pharmacology
  • Potassium / metabolism
  • Potassium / pharmacology
  • Potassium Channels / metabolism
  • Rabbits
  • ortho-Aminobenzoates / pharmacology


  • Anions
  • Bicarbonates
  • Butyrates
  • Chloride Channels
  • Chlorides
  • Gluconates
  • Ion Channels
  • Isobutyrates
  • Membrane Proteins
  • Nitrobenzoates
  • Potassium Channels
  • ortho-Aminobenzoates
  • Carbon Dioxide
  • 3',5-dichlorodiphenylamine-2-carboxylic acid
  • 5-nitro-2-(3-phenylpropylamino)benzoic acid
  • Amiloride
  • isobutyric acid
  • fenamic acid
  • Diphenylamine
  • gluconic acid
  • Nigericin
  • Potassium