Anion secretion by the inner medullary collecting duct. Evidence for involvement of the cystic fibrosis transmembrane conductance regulator

J Clin Invest. 1995 Feb;95(2):644-50. doi: 10.1172/JCI117709.

Abstract

It is well established that the terminal renal collecting duct is capable of electrogenic Na+ absorption. The present experiments examined other active ion transport processes in primary cultures of the rat inner medullary collecting duct. When the amiloride analogue benzamil inhibited electrogenic Na+ absorption, cAMP agonists stimulated a transmonolayer short circuit current that was not dependent on the presence of Na+ in the apical solution, but was dependent on the presence of Cl- and HCO3-. This current was not inhibited by the loop diuretic bumetanide, but was inhibited by ouabain, an inhibitor of the Na+/K+ pump. The current was reduced by anion transport inhibitors, with a profile similar to that seen for inhibitors of the cystic fibrosis transmembrane conductance regulator (CFATR) Cl- channel. Using several PCR strategies, we demonstrated fragments of the predicted lengths and sequence identity with the rat CFTR. Using whole-cell patch-clamp analysis, we demonstrated a cAMP-stimulated Cl- current with characteristics of the CFTR. We conclude that the rat inner medullary collecting duct has the capacity to secrete anions. It is highly likely that the CFTR Cl- channel is involved in this process.

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

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Amiloride / analogs & derivatives
  • Amiloride / pharmacology
  • Analysis of Variance
  • Animals
  • Anions / metabolism
  • Base Sequence
  • Bicarbonates / metabolism
  • Bumetanide / pharmacology
  • Cells, Cultured
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / physiology*
  • Chlorides / metabolism*
  • Chlorides / pharmacology
  • Cyclic AMP / physiology
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • DNA Primers
  • Epithelium / drug effects
  • Epithelium / physiology
  • Female
  • Glyburide / pharmacology
  • Glycolates / pharmacology
  • Kidney Medulla / drug effects
  • Kidney Medulla / physiology*
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / physiology*
  • Kinetics
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Nitrobenzoates / pharmacology
  • Ouabain / pharmacology
  • Patch-Clamp Techniques
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar

Substances

  • Anions
  • Bicarbonates
  • Chloride Channels
  • Chlorides
  • DNA Primers
  • Glycolates
  • Membrane Proteins
  • Nitrobenzoates
  • benzamil
  • Bumetanide
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • 5-nitro-2-(3-phenylpropylamino)benzoic acid
  • MK 473
  • Ouabain
  • Amiloride
  • Cyclic AMP
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • Glyburide
  • 1-Methyl-3-isobutylxanthine