Journal article
Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel
The Journal of clinical investigation, Vol.88(4), pp.1422-1431
10/1991
DOI: 10.1172/JCI115450
PMCID: PMC295615
PMID: 1717515
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) generates cAMP-regulated Cl- channels; mutations in CFTR cause defective Cl- channel function in cystic fibrosis epithelia. We used the patch-clamp technique to determine the single channel properties of Cl- channels in cell expressing recombinant CFTR. In cell-attached patches, an increase in cellular cAMP reversibly activated low conductance Cl- channels. cAMP-dependent regulation is due to phosphorylation, because the catalytic subunit of cAMP-dependent protein kinase plus ATP reversibly activated the channel in excised, cell-free patches of membrane. In symmetrical Cl- solutions, the channel had a channel conductance of 10.4 +/- 0.2 (n = 7) pS and a linear current-voltage relation. The channel was more permeable to Cl- than to I- and showed no appreciable time-dependent voltage effects. These biophysical properties are consistent with macroscopic studies of Cl- channels in single cells expressing CFTR and in the apical membrane of secretory epithelia. Identification of the single channel characteristics of CFTR-generated channels allows further studies of their regulation and the mechanism of ion permeation.
Details
- Title: Subtitle
- Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel
- Creators
- Herbert A Berger - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Michael P Anderson - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Richard J Gregory - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Simon Thompson - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Paul W Howard - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Richard A Maurer - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Richard Mulligan - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Alan E Smith - 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
- The Journal of clinical investigation, Vol.88(4), pp.1422-1431
- DOI
- 10.1172/JCI115450
- PMID
- 1717515
- PMCID
- PMC295615
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 10/1991
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020619402771
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