Maximization of the rate of chloride conduction in the CFTR channel pore by ion-ion interactions.
Multi-ion pore behaviour has been identified in many Cl(-) channel types but its biophysical significance is uncertain. Here, we show that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel that disrupt anion-anion interactions within the pore are associated with drastically reduced single channel conductance. These results are consistent with models suggesting that rapid Cl(-) permeation in CFTR results from repulsive ion-ion interactions between Cl(-) ions bound concurrently inside the pore. Naturally occurring mutations that disrupt these interactions can result in cystic fibrosis.
Gong
Xiandi
X
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada B3H 1X5.
Linsdell
Paul
P
D019943:Amino Acid Substitution; D000818:Animals; D000838:Anions / Q000378:metabolism; D002460:Cell Line; D002712:Chlorides / Q000737:chemistry / Q000378:metabolism*; D006224:Cricetinae; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D010539:Permeability; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000838:Anions; C505032:CFTR protein, human; D002712:Chlorides; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator