Permeability of Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels to Polyatomic Anions

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 (PX/PCl) 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 (PX/PCl < 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 anions, but may contribute to the narrowest part of the pore.

• Publication year

  1997

• Venue

  The Journal of General Physiology

• Publication date

  1997-10-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1085/JGP.110.4.355PMID 9379168PMCID 2229373
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  1997influential reference
• Failure of the Cystic Fibrosis Transmembrane Conductance Regulator to Conduct ATP

  1996cited by this paper
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  1996influential reference
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  1996cited by this paper
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  1995cited by this paper
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  1995cited by this paper
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  1994influential reference
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  1994cited by this paper
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  1994influential reference
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  1990cited by this paper
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  1989cited by this paper
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  1980influential reference
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  1977influential reference

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