CFTR Regulates Outwardly Rectifying Chloride Channels Through an Autocrine Mechanism Involving ATP

Cell. 1995 Jun 30;81(7):1063-73. doi: 10.1016/s0092-8674(05)80011-x.

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) functions to regulate both Cl- and Na+ conductive pathways; however, the cellular mechanisms whereby CFTR acts as a conductance regulator are unknown. CFTR and outwardly rectifying Cl- channels (ORCCs) are distinct channels but are linked functionally via an unknown regulatory mechanism. We present results from whole-cell and single-channel patch-clamp recordings, short-circuit current recordings, and [gamma-32P]ATP release assays of normal, CF, and wild-type or mutant CFTR-transfected CF airway cultured epithelial cells wherein CFTR regulates ORCCs by triggering the transport of the potent agonist, ATP, out of the cell. Once released, ATP stimulates ORCCs through a P2U purinergic receptor-dependent signaling mechanism. Our results suggest that CFTR functions to regulate other Cl- secretory pathways in addition to itself conducting Cl-.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Adenosine Triphosphate / pharmacology
  • Cell Line
  • Chloride Channels / drug effects
  • Chloride Channels / physiology*
  • Cyclic AMP / metabolism*
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Epithelium / physiology
  • Homeostasis
  • Humans
  • Membrane Potentials / drug effects
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Models, Structural
  • Patch-Clamp Techniques
  • Recombinant Proteins / metabolism
  • Trachea / physiology*
  • Trachea / physiopathology
  • Transfection

Substances

  • CFTR protein, human
  • Chloride Channels
  • Membrane Proteins
  • Recombinant Proteins
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Adenosine Triphosphate
  • Cyclic AMP