Wild type but not deltaF508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes.
Airway epithelial cells bearing mutations of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) possess an increased Na+ conductance along with their well described defect of cAMP dependent Cl- conductance. Currently it is not clear, how this occurs, and whether it is due to a CFTR control of epithelial Na+ conductances which might be defective in CF patients. In the present study, we have tried to identify possible interactions between both CFTR and the epithelial Na+ conductance by overexpressing respective cRNAs in Xenopus oocytes. The expression of all three (alpha, beta, gamma) subunits of the rat epithelial Na+ channel (rENaC) and wild type (wt) CFTR resulted in the expected amiloride sensitive Na+ and IBMX (1 mmol/l) activated Cl- currents, respectively. The amiloride sensitive Na+ conductance was, however, inhibited when the wt-CFTR Cl- conductance was activated by phosphodiesterase inhibition (IBMX). In contrast, IBMX had no such effect in deltaF508 and Na+ channels coexpressing oocytes. These results suggest that wt-CFTR, but not deltaF508-CFTR, is a cAMP dependent downregulator of epithelial Na+ channels. This may explain the higher Na+ conductance observed in airway epithelial cells of CF patients.
Mall
M
M
Physiologisches Institut der Albert-Ludwigs-Universität Freiburg, Germany.
Hipper
A
A
Greger
R
R
Kunzelmann
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D003001:Cloning, Molecular; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D008536:Meglumine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology*; D018408:Patch-Clamp Techniques; D018075:RNA, Complementary; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000096:biosynthesis / Q000502:physiology*; D014982:Xenopus laevis
D002712:Chlorides; D018075:RNA, Complementary; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D008536:Meglumine; D000584:Amiloride; D012964:Sodium; D015056:1-Methyl-3-isobutylxanthine