Regulation of epithelial sodium channels by the cystic fibrosis transmembrane conductance regulator.

Academic Article

Abstract

  • Cystic fibrosis airway epithelia exhibit enhanced Na+ reabsorption in parallel with diminished Cl- secretion. We tested the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) directly affects epithelial Na+ channel activity by co-incorporating into planar lipid bilayers immunopurified bovine tracheal CFTR and either heterologously expressed rat epithelial Na+ channel ( alpha,b eta,gamma-rENaC) or an immunopurified bovine renal Na+ channel protein complex. The single channel open probability (Po) of rENaC was decreased by 24% in the presence of CFTR. Protein kinase A (PKA) plus ATP activated CFTR, but did not have any effect on rENaC. CFTR also decreased the extent of elevation of the renal Na+ channel Po following PKA-mediated phosphorylation. Moreover, the presence of CFTR prohibited the inward rectification of the gating of this renal Na+ channel normally induced by PKA-mediated phosphorylation, thus down-regulating inward Na+ current. This interaction between CFTR and Na+ channels occurs independently of whether or not wild-type CFTR is conducting anions. However, the nonconductive CFTR mutant, G551D CFTR, cannot substitute for the wild-type molecule. Our results indicate that CFTR can directly down-regulate single Na+ channel activity, thus accounting, at least in part, for the observed differences in Na+ transport between normal and cystic fibrosis-affected airway epithelia.
  • Published In

    Keywords

  • Adenosine Triphosphate, Amiloride, Animals, Cattle, Cell Membrane, Cystic Fibrosis Transmembrane Conductance Regulator, Electric Conductivity, Epithelium, Female, Gene Expression, Ion Channel Gating, Kidney Medulla, Lipid Bilayers, Membrane Potentials, Oocytes, Phosphorylation, Point Mutation, Protein Kinases, Recombinant Proteins, Sodium Channels
  • Author List

  • Ismailov II; Awayda MS; Jovov B; Berdiev BK; Fuller CM; Dedman JR; Kaetzel M; Benos DJ
  • Start Page

  • 4725
  • End Page

  • 4732
  • Volume

  • 271
  • Issue

  • 9