Permeability of Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels to Polyatomic Anions
| Autor: | Lap-Chee Tsui, Xiu Bao Chang, Yue Xian Hou, J. A. Tabcharani, John W. Hanrahan, Paul Linsdell, Johanna M. Rommens, John R. Riordan |
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| Rok vydání: | 1997 |
| Předmět: |
Anions
Patch-Clamp Techniques Physiology Molecular Sequence Data Inorganic chemistry Cystic Fibrosis Transmembrane Conductance Regulator CHO Cells Article Permeability Cystic fibrosis Membrane Potentials Anions - metabolism Channel selectivity Lyotropic sequence Cricetinae Animals Cystic fibrosis transmembrane conductance regulator - genetics - metabolism Amino Acid Sequence Patch clamp Gene expression regulation Anion permeation biology Chemistry Polyatomic ion Membrane potentials - physiology Conductance Methane sulfonate Ion channel gating - genetics - physiology Cystic fibrosis transmembrane conductance regulator Membrane Mutagenesis Permeability (electromagnetism) Pore size Chloride channel Biophysics biology.protein Ion Channel Gating |
| Zdroj: | The Journal of General Physiology |
| ISSN: | 1540-7748 0022-1295 |
| DOI: | 10.1085/jgp.110.4.355 |
| Popis: | 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. published_or_final_version |
| Databáze: | OpenAIRE |
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