Transepithelial fluctuation analysis of chloride secretion

J Cyst Fibros. 2004 Aug:3 Suppl 2:127-32. doi: 10.1016/j.jcf.2004.05.027.

Abstract

Transepithelial fluctuation analysis (noise analysis) provides valuable information about the density and single-channel properties of ion channels in intact epithelia. Here we investigate cystic fibrosis transmembrane conductance regulator (CFTR)-dependent chloride (Cl-) secretion in T84 human colonic epithelia by inducing noise using the diarylsulfonylurea DASU-01, a low-affinity open-channel blocker of CFTR. Our data indicate that the apical membrane of maximally stimulated T84 epithelia has a very high Cl- conductance generated by approximately 7000 active CFTR channels per cell with open probability (Po) of approximately 0.4 and single-channel amplitude (i) of approximately 0.1 pA. Similar experiments might provide important information about how drugs regulate CFTR in intact epithelia.

Publication types

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

MeSH terms

  • Cell Membrane / metabolism
  • Cells, Cultured
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism*
  • Chlorides / analysis
  • Chlorides / metabolism*
  • Colon / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
  • Cystic Fibrosis Transmembrane Conductance Regulator / drug effects
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism
  • Models, Biological
  • Patch-Clamp Techniques / methods*
  • Sulfonylurea Compounds / pharmacology

Substances

  • CFTR protein, human
  • Chloride Channels
  • Chlorides
  • Sulfonylurea Compounds
  • Cystic Fibrosis Transmembrane Conductance Regulator