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Updated: Nov 4, 2025
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Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
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Monovalent: Divalent Anion Selectivity in the CFTR Channel Pore
1Department of Physiology & Biophysics, Dalhousie University, Halifax, NS, Canada. paul.linsdell@dal.ca.
Cell Biochemistry and Biophysics
|May 25, 2021
Summary
Cystic fibrosis transmembrane conductance regulator (CFTR) channels poorly bind and permeate divalent anions like thiosulfate and sulfate. Pore mutations enhancing positive charge increase divalent anion block, indicating CFTR favors monovalent chloride ions.
Area of Science:
- Ion channel biophysics
- Molecular physiology
- Membrane transport
Background:
- Cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial chloride channel.
- CFTR exhibits weak selectivity among small monovalent anions.
- CFTR's discrimination between monovalent and divalent anions remains poorly understood.
Purpose of the Study:
- To investigate the interaction of divalent anions (thiosulfate, sulfate) with CFTR.
- To determine CFTR's ability to discriminate between monovalent and divalent anions.
- To analyze the role of pore charge in divalent anion interaction with CFTR.
Main Methods:
- Patch clamp electrophysiology on wild-type and mutant human CFTR channels.
- Assessment of anion block and permeability using specific divalent anions.
- Voltage-dependent analysis of anion binding affinities.
Main Results:
- Wild-type CFTR showed weak block by intracellular thiosulfate (<20%) and sulfate (<5%) at 10 mM.
- Mutations (I344K, S1141K) introducing positive charge in the pore significantly enhanced intracellular divalent anion block.
- Divalent anion permeability through wild-type and mutant CFTR was immeasurably low, less than 1% of chloride permeability.
Conclusions:
- CFTR demonstrates strong selectivity for monovalent over divalent anions in both binding and permeability.
- The pore's positive charge density is optimized to disfavor divalent anion binding.
- This selectivity is a key aspect of CFTR's physiological function in chloride transport.
Keywords:
Anion selectivityChloride channelCystic fibrosis transmembrane conductance regulatorDivalent anionsIon bindingIon permeationMore Related Videos
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