K channel gating by an affinity-switching selectivity filter.
A universal property of ion channels is their ability to alternate stochastically between two permeation states, open and closed. This behavior is thought to be controlled by a steric "gate", a structure that physically impedes ion flow in the closed state and moves out of the way during channel opening. Experiments employing macroscopic currents in the Shaker K channel have suggested a cytoplasmic localization for the gate. Crystallographic structures of the KcsA K channel indeed reveal a cytoplasmic constriction, implying that the gate and selectivity filter are localized to opposite ends of the permeation pathway. However, analysis of K channel subconductance behavior has suggested a strict coupling between channel opening (gating) and permeation. The idea that the selectivity filter is the gate was therefore investigated by using Monte Carlo simulations. Gating is accomplished by allowing the filter to alternate stochastically between two conformations: a high-affinity state, which selectively binds K ions (but not Na ions) and traps them, and a completely nonselective, low-affinity state, which allows both Na and K ions to permeate. The results of these simulations indicate that affinity switching not only endows the selectivity filter with gating abilities, it also allows efficient permeation without jeopardizing ion selectivity. In this model, permeation and gating result from the same process.
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Related Subject Headings
- Shaker Superfamily of Potassium Channels
- Potassium Channels
- Permeability
- Monte Carlo Method
- Models, Biological
- Kinetics
- Ion Channel Gating
- Crystallography, X-Ray
- Computer Simulation
- Algorithms
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Shaker Superfamily of Potassium Channels
- Potassium Channels
- Permeability
- Monte Carlo Method
- Models, Biological
- Kinetics
- Ion Channel Gating
- Crystallography, X-Ray
- Computer Simulation
- Algorithms