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.
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1 October 1997
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October 01 1997
Permeability of Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels to Polyatomic Anions
Paul Linsdell,
Paul Linsdell
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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Joseph A. Tabcharani,
Joseph A. Tabcharani
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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Johanna M. Rommens,
Johanna M. Rommens
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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Yue-Xian Hou,
Yue-Xian Hou
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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Xiu-Bao Chang,
Xiu-Bao Chang
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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Lap-Chee Tsui,
Lap-Chee Tsui
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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John R. Riordan,
John R. Riordan
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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John W. Hanrahan
John W. Hanrahan
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
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Paul Linsdell
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
Joseph A. Tabcharani
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
Johanna M. Rommens
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
Yue-Xian Hou
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
Xiu-Bao Chang
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
Lap-Chee Tsui
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
John R. Riordan
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
John W. Hanrahan
From the *Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada; ‡Department of Genetics, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8; and §S.C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
Address correspondence to John W. Hanrahan, Department of Physiology, McGill University, 3655 Drummond St., Montréal, Québec H3G 1Y6, Canada. Fax: 514-398-7452; E-mail: [email protected]
Received:
October 10 1996
Accepted:
July 11 1997
Online ISSN: 1540-7748
Print ISSN: 0022-1295
1997
J Gen Physiol (1997) 110 (4): 355–364.
Article history
Received:
October 10 1996
Accepted:
July 11 1997
Citation
Paul Linsdell, Joseph A. Tabcharani, Johanna M. Rommens, Yue-Xian Hou, Xiu-Bao Chang, Lap-Chee Tsui, John R. Riordan, John W. Hanrahan; Permeability of Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels to Polyatomic Anions . J Gen Physiol 1 October 1997; 110 (4): 355–364. doi: https://doi.org/10.1085/jgp.110.4.355
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