Control of epithelial ion transport by Cl- and PDZ proteins.
Inhibition of epithelial Na+ channels (ENaC) by the cystic fibrosis transmembrane conductance regulator (CFTR) has been demonstrated previously. Recent studies suggested a role of cytosolic Cl- for the interaction of CFTR with ENaC, when studied in Xenopus oocytes. In the present study we demonstrate that the Na+ / H+ -exchanger regulator factor (NHERF) controls expression of CFTR in mouse collecting duct cells. Inhibition of NHERF largely attenuates CFTR expression, which is paralleled by enhanced Ca(2+) -dependent Cl- secretion and augmented Na+ absorption by the ENaC. It is further demonstrated that epithelial Na+ absorption and ENaC are inhibited by cytosolic Cl- and that stimulation by secretagogues enhances the intracellular Cl- concentration. Thus, the data provide a clue to the question, how epithelial cells can operate as both absorptive and secretory units: Increase in intracellular Cl- during activation of secretion will inhibit ENaC and switch epithelial transport from salt absorption to Cl- secretion.
Schreiber
R
R
Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany.
Boucherot
A
A
Mürle
B
B
Sun
J
J
Kunzelmann
K
K
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D053503:Epithelial Sodium Channels; D006706:Homeostasis / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D053503:Epithelial Sodium Channels; D010750:Phosphoproteins; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002713:Chlorine; D012964:Sodium