Journal article
Fluoride stimulates cystic fibrosis transmembrane conductance regulator Cl− channel activity
American journal of physiology. Lung cellular and molecular physiology, Vol.274(3), pp.L305-L312
03/01/1998
DOI: 10.1152/ajplung.1998.274.3.L305
PMID: 9530164
Abstract
While studying the regulation of the cystic fibrosis transmembrane conductance regulator (CFTR), we found that addition of F− to the cytosolic surface of excised, inside-out membrane patches reversibly increased Cl− current in a dose-dependent manner. Stimulation required prior phosphorylation and the presence of ATP. F− increased current even in the presence of deferoxamine, which chelates Al3+, suggesting that stimulation was not due to A[Formula: see text]. F− also stimulated current in a CFTR variant that lacked a large part of the R domain, suggesting that the effect was not mediated via this domain. Studies of single channels showed that F−increased the open-state probability by slowing channel closure from bursts of activity; the mean closed time between bursts and single-channel conductance was not altered. These results suggested that F− influenced regulation by the cytosolic domains, most likely the nucleotide-binding domains (NBDs). Consistent with this, we found that mutation of a conserved Walker lysine in NBD2 changed the relative stimulatory effect of F− compared with wild-type CFTR, whereas mutation of the Walker lysine in NBD1 had no effect. Based on these and previous data, we speculate that F− interacts with CFTR, possibly via NBD2, and slows the rate of channel closure.
Details
- Title: Subtitle
- Fluoride stimulates cystic fibrosis transmembrane conductance regulator Cl− channel activity
- Creators
- Herbert A Berger - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242Sue M Travis - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242Michael J Welsh - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.274(3), pp.L305-L312
- DOI
- 10.1152/ajplung.1998.274.3.L305
- PMID
- 9530164
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Publisher
- American Physiological Society
- Language
- English
- Date published
- 03/01/1998
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020701102771
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