CFTR-mediated inhibition of epithelial Na+ conductance in human colon is defective in cystic fibrosis

Am J Physiol. 1999 Sep;277(3):G709-16. doi: 10.1152/ajpgi.1999.277.3.G709.


Cystic fibrosis (CF) patients show characteristic defects in epithelial ion transport, such as failure in cAMP-dependent Cl- secretion. Because the cystic fibrosis transmembrane conductance regulator (CFTR) also functions as a downregulator of epithelial Na+ channels (ENaC), enhanced Na+ conductance was found in the airways of CF patients. Here, we examined whether enhanced epithelial Na+ conductance is also present in the colonic epithelium of CF patients and examined the underlying mechanisms. Thus transepithelial voltages were measured, and equivalent short-circuit currents (I(sc-eq)) were determined by means of a novel type of Ussing chamber. Non-CF tissues demonstrated cAMP-dependent Cl- secretion that was absent in biopsies of CF patients. Correspondingly, Isc-eq was inhibited in non-CF but not in CF epithelia when synthesis of endogenous prostaglandins was blocked by indomethacin. In the presence of indomethacin, a larger portion of amiloride-sensitive Isc-eq was detected in CF tissues, suggesting enhanced ENaC conductance in colonic mucosa of CF patients. Increase of intracellular cAMP by forskolin and IBMX inhibited amiloride-sensitive ENaC currents in non-CF tissues but not in CF biopsies. Therefore, enhanced epithelial Na+ conductance is present in the CF colon and is probably due to missing downregulation by CFTR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Colon / metabolism*
  • Cyclic AMP / physiology
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Electric Conductivity
  • Epithelial Sodium Channels
  • Humans
  • Infant
  • Infant, Newborn
  • Intestinal Mucosa / metabolism
  • Ion Transport
  • Middle Aged
  • Rectum / metabolism
  • Reference Values
  • Sodium / physiology
  • Sodium Channel Blockers*
  • Sodium Channels*


  • CFTR protein, human
  • Epithelial Sodium Channels
  • Sodium Channel Blockers
  • Sodium Channels
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Sodium
  • Cyclic AMP