cAMP stimulation of CFTR-expressing Xenopus oocytes activates a chromanol-inhibitable K+ conductance.
Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a Cl- channel in a large variety of cells expressing this protein. Recently evidence has accumulated that it also regulates other ion channels. A coordinated increase in Cl- and K+ conductances is necessary in many Cl--secreting epithelia. This has, for example, recently been demonstrated for the colonic crypt, for which a new type of K+ channel and a specific inhibitor of this channel, the chromanol 293B, have been described. In the present study we have examined whether the cAMP-evoked activation of CFTR, overexpressed in Xenopus oocytes, in addition to its known activation of a Cl- conductance, also upregulates endogenous K+ channels. It is shown that CFTR-cRNA-injected but not water-injected oocytes possess a cAMP-activated Cl- conductance. Of the cAMP-induced whole-cell current increase, 15-25% was due to a 293B-, Ba2+and TEA+-inhibitable K+ conductance. The cRNA of the mutated CFTR (DeltaF508 CFTR) had no such effect. We conclude that cAMP activated CFTR and an endogenous IsK-type and 293B-sensitive K+ conductance. Similar events, occurring, for example, in the colonic crypt possessing CFTR and 293B-sensitive K+ channels, might explain the coordinated cAMP-mediated increase in Cl- and K+ conductances.
Mall
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M
Physiologisches Institut der Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
Kunzelmann
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K
Hipper
A
A
Busch
A E
AE
Greger
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014982:Xenopus laevis
D000975:Antioxidants; D002839:Chromans; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D013873:Thionucleotides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine