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

H. A. Berger, M. P. Anderson, R. J. Gregory, S. Thompson, P. W. Howard, R. A. Maurer, R. Mulligan, A. E. Smith, M. J. Welsh

Research output: Contribution to journalArticle

170 Scopus citations

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
DOIs
StatePublished - Jan 1 1991

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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    Berger, H. A., Anderson, M. P., Gregory, R. J., Thompson, S., Howard, P. W., Maurer, R. A., Mulligan, R., Smith, A. E., & 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. https://doi.org/10.1172/JCI115450