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 (α,β,γ-rENaC) or an immunopurified bovine renal Na+ channel protein complex. The single channel open probability (P(o)) 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 P(o) 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

    Digital Object Identifier (doi)

    Author List

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

  • 4725
  • End Page

  • 4732
  • Volume

  • 271
  • Issue

  • 9