Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions

Paul Linsdell, Joseph A. Tabcharani, Johanna M. Rommens, Yue Xian Hou, Xiu Bao Chang, Lap Chee Tsui, John R. Riordan, John W. Hanrahan

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158 Scopus citations

Abstract

Permeability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel to polyatomic anions of known dimensions was studied in stably transfected Chinese hamster ovary cells by using the patch clamp technique. Biionic reversal potentials measured with external polyatomic anions gave the permeability ratio (P(X)/P(Cl)) sequence NO3/- > Cl- > HCO3/- > formate > acetate. The same selectivity sequence but somewhat higher permeability ratios were obtained when anions were tested from the cytoplasmic side. Pyruvate, propanoate, methane sulfonate, ethane sulfonate, and gluconate were not measurably permeant (P(X)/P(Cl) < 0.06) from either side of the membrane. The relationship between permeability ratios from the outside and ionic diameters suggests a minimum functional pore diameter of ~5.3 Å. Permeability ratios also followed a lyotropic sequence, suggesting that permeability is dependent on ionic hydration energies. Site-directed mutagenesis of two adjacent threonines in TM6 to smaller, less polar alanines led to a significant (24%) increase in single channel conductance and elevated permeability to several large anions, suggesting that these residues do not strongly bind permeating artions, but may contribute to the narrowest part of the pore.

Original languageEnglish (US)
Pages (from-to)355-364
Number of pages10
JournalJournal of General Physiology
Volume110
Issue number4
DOIs
StatePublished - Oct 1997

Keywords

  • Anion permeation
  • Channel selectivity
  • Cystic fibrosis
  • Lyotropic sequence
  • Pore size

ASJC Scopus subject areas

  • Physiology

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    Linsdell, P., Tabcharani, J. A., Rommens, J. M., Hou, Y. X., Chang, X. B., Tsui, L. C., Riordan, J. R., & Hanrahan, J. W. (1997). Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions. Journal of General Physiology, 110(4), 355-364. https://doi.org/10.1085/jgp.110.4.355