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Permeability properties of ENaC selectivity filter mutants.
S Kellenberger1, M Auberson, I Gautschi
1Institut de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland. stephan.kellenberger@ipharm.unil.ch
The Journal of General Physiology
|November 28, 2001
Summary
Mutations in the epithelial sodium channel (ENaC) at the alphaS589 residue enlarge the ion selectivity filter. This pore size change alters ion permeability, impacting sodium absorption in epithelia.
Area of Science:
- Molecular Biology
- Biophysics
- Physiology
Background:
- The epithelial sodium channel (ENaC) is crucial for sodium absorption in tight epithelia.
- ENaC is highly selective for sodium (Na+) and lithium (Li+) ions.
- The preM2 segment of ENaC is implicated in forming the outer pore and ion selectivity.
Purpose of the Study:
- To investigate the molecular basis of altered ion selectivity in ENaC.
- To determine the role of the alphaS589 residue in the preM2 segment on channel pore properties.
Main Methods:
- Site-directed mutagenesis of the alphaS589 residue in ENaC.
- Electrophysiological analysis of mutant channel function.
- Assessment of ion permeability and conductance.
Main Results:
- Increasing the size of the amino acid at alphaS589 enlarged the channel's molecular cutoff for cations.
- Mutations at alphaS589 increased permeability to larger cations.
- Larger pore mutants exhibited reduced unitary conductance for Na+ and Li+.
Conclusions:
- The pore size at the alphaS589 residue is critical for ENaC's ion selectivity.
- AlphaS589 side chains likely face the subunit-subunit interface, influencing pore diameter.
- ENaC pore enlargement at alphaS589 affects selectivity and conductance properties.