Coupling of CFTR Cl- channel gating to an ATP hydrolysis cycle.
For cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels to open, they must be phosphorylated by protein kinase A and then exposed to a hydrolyzable nucleoside triphosphate, such as ATP. To test whether channel opening is linked to ATP hydrolysis, we applied VO4 and BeF3 to CFTR channels in inside-out patches excised from cardiac myocytes. These inorganic phosphate analogs interrupt ATP hydrolysis cycles by binding tightly in place of the released hydrolysis product, inorganic phosphate. The analogs acted only on CFTR channels opened by ATP and locked them open, increasing their mean open time by 2-3 orders of magnitude. These findings establish that opening and closing of CFTR channels are coupled to an ATP hydrolysis cycle.
Baukrowitz
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Laboratory of Cardiac/Membrane Physiology, Rockefeller University, New York, New York 10021.
Hwang
T C
TC
Nairn
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AC
Gadsby
D C
DC
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001608:Beryllium / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D006168:Guinea Pigs; D006868:Hydrolysis; D015640:Ion Channel Gating; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014638:Vanadates; C035982:beryllium fluoride; D000255:Adenosine Triphosphate; D001608:Beryllium; D005459:Fluorides