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J. Biol. Chem., Vol. 276, Issue 9, 6473-6478, March 2, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/9/6473    most recent M009305200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, J. V. Articles by Wine, J. J. Search for Related Content PubMed PubMed Citation Articles by Wu, J. V. Articles by Wine, J. J. Social Bookmarking                      What's this?

Cystic Fibrosis Transmembrane Conductance Regulator Gating Requires Cytosolic Electrolytes^*

Jin V. Wu, Nam Soo Joo, Mauri E. Krouse, and Jeffrey J. Wine

From the Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California 94305-2130

Cystic fibrosis transmembrane conductance regulator (CFTR), which causes cystic fibrosis when nonfunctional, is an anion channel and a member of the ATP binding cassette superfamily. After phosphorylation, CFTR gates by binding and hydrolyzing ATP. We show that CFTR open probability (P_o) also depends on the electrolyte concentration of the cytosol. Inside-out patches from Calu-3 cells were transiently exposed to solutions of 160 mM salt or solutions in which up to 90% of the salt was replaced by nonionic osmolytes such as sucrose. In lowered salt solutions, CFTR P_o declined within 1 s to a stable lower value that depended on the electrolyte concentration, (K_1/2  80 mM NaCl). P_o was rapidly restored in normal salt concentrations without regard to the electrolyte species. Reducing external electrolytes did not affect CFTR P_o. The same results were obtained when CFTR was stably phosphorylated with adenosine 5'-O-(thiotriphosphate). The decrease in P_o resulted entirely from an increase in mean closed time. Increasing ATP levels up to 20-fold did not counteract the effect of low electrolytes. The same effect was observed for CFTR expressed in C127 cells but not for a different species of anion channel. Cytosolic electrolytes are an unsuspected, essential cofactor for CFTR gating.

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