Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel

Herbert A. Berger, Matthew P. Andersen, Richard J. Gregory, Simon Thompson, Paul W. Howard, Richard Maurer, Richard Mulligan, Alan E. Smith, Michael J. Welsh

Research output: Contribution to journalArticle

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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 cells 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.

Original languageEnglish (US)
Pages (from-to)1422-1431
Number of pages10
JournalJournal of Clinical Investigation
Volume88
Issue number4
StatePublished - 1991
Externally publishedYes

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Epithelium
Membranes
Patch-Clamp Techniques
Cyclic AMP-Dependent Protein Kinases
Cystic Fibrosis
Catalytic Domain
Adenosine Triphosphate
Phosphorylation
Ions
Mutation

Keywords

  • cAMP
  • CT secretion
  • Cystic fibrosis
  • Patch-clamp
  • Phosphorylation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Berger, H. A., Andersen, M. P., Gregory, R. J., Thompson, S., Howard, P. W., Maurer, R., ... Welsh, M. J. (1991). Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel. Journal of Clinical Investigation, 88(4), 1422-1431.

Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel. / Berger, Herbert A.; Andersen, Matthew P.; Gregory, Richard J.; Thompson, Simon; Howard, Paul W.; Maurer, Richard; Mulligan, Richard; Smith, Alan E.; Welsh, Michael J.

In: Journal of Clinical Investigation, Vol. 88, No. 4, 1991, p. 1422-1431.

Research output: Contribution to journalArticle

Berger, HA, Andersen, MP, Gregory, RJ, Thompson, S, Howard, PW, Maurer, R, Mulligan, R, Smith, AE & Welsh, MJ 1991, 'Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel', Journal of Clinical Investigation, vol. 88, no. 4, pp. 1422-1431.
Berger, Herbert A. ; Andersen, Matthew P. ; Gregory, Richard J. ; Thompson, Simon ; Howard, Paul W. ; Maurer, Richard ; Mulligan, Richard ; Smith, Alan E. ; Welsh, Michael J. / Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel. In: Journal of Clinical Investigation. 1991 ; Vol. 88, No. 4. pp. 1422-1431.
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AB - 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 cells 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.

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