Journal article
Phosphate stimulates CFTR Cl- channels
Biophysical journal, Vol.67(5), pp.1867-1875
11/1994
DOI: 10.1016/S0006-3495(94)80668-X
PMCID: PMC1225560
PMID: 7532021
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels appear to be regulated by hydrolysis of ATP and are inhibited by a product of hydrolysis, ADP. We assessed the effect of the other product of hydrolysis, inorganic phosphate (P(i)), on CFTR Cl- channel activity using the excised inside-out configuration of the patch-clamp technique. Millimolar concentrations of P(i) caused a dose-dependent stimulation of CFTR Cl- channel activity. Single-channel analysis demonstrated that the increase in macroscopic current was due to an increase in single-channel open-state probability (po) and not single-channel conductance. Kinetic modeling of the effect of P(i) using a linear three-state model indicated that the effect on po was predominantly the result of an increase in the rate at which the channel passed from the long closed state to the bursting state. P(i) also potentiated activity of channels studied in the presence of 10 mM ATP and stimulated Cl- currents in CFTR mutants lacking much of the R domain. Binding studies with a photoactivatable ATP analog indicated that Pi decreased the amount of bound nucleotide. These results suggest that P(i) increased CFTR Cl- channel activity by stimulating a rate-limiting step in channel opening that may occur by an interaction of P(i) at one or both nucleotide-binding domains.
Details
- Title: Subtitle
- Phosphate stimulates CFTR Cl- channels
- Creators
- Mark R Carson - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Sue M Travis - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Michael C Winter - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242David N Sheppard - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Michael J. Welsh - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
- Resource Type
- Journal article
- Publication Details
- Biophysical journal, Vol.67(5), pp.1867-1875
- DOI
- 10.1016/S0006-3495(94)80668-X
- PMID
- 7532021
- PMCID
- PMC1225560
- ISSN
- 0006-3495
- eISSN
- 1542-0086
- Language
- English
- Date published
- 11/1994
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020648402771
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