A constricted opening in Kir channels does not impede potassium conduction
Katrina A Black1,2, Sitong He3, Ruitao Jin3
1Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Nature Communications
|June 17, 2020
Summary
Potassium channel gating may not rely on conformational changes. Instead, permeation of potassium ions through Kir channels occurs via partial dehydration, challenging the canonical model.
Area of Science:
- Biophysics
- Molecular Biology
- Ion Channel Physiology
Background:
- The canonical model for potassium channel gating involves conformational changes at the intracellular entrance to accommodate hydrated ions.
- This model assumes potassium (K+) ions retain their full hydration shell during transit.
Purpose of the Study:
- To test the canonical model of potassium channel gating.
- To investigate the mechanism of ion permeation through Kir channels.
Main Methods:
- Engineered a Kir K+ channel mutant with a locked conformation to prevent pore dilation.
- Utilized all-atom molecular dynamics simulations to observe K+ ion movement and hydration state.
Main Results:
- Potassium ion conduction remained unimpaired in the locked Kir channel mutant.
- Simulations revealed that K+ permeation occurred with transient water molecule displacement, not significant pore widening.
- A low free energy barrier for partial dehydration was observed.
Conclusions:
- The canonical gating mechanism involving significant conformational changes is not essential for Kir channel function.
- Potassium ion permeation through Kir channels is facilitated by partial dehydration at the intracellular entrance.
- These findings necessitate a revision of the current understanding of potassium channel gating mechanisms.
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