Allosteric Effects of Permeating Cations on Gating Currents during K+ Channel Deactivation
Population
Human embryonic kidney cells highly overexpressing the voltage-gated K+ channel Kv1.5
Comparison
Presence of permeating cations (K+ or Cs+) vs Absence of permeant ions
Design
Preclinical
Authors
Discussion
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Member takes
Implication
May refine models of channel availability during repetitive firing; leaves open relevance to native cardiac electrophysiology.
Key Points
- To investigate how permeating potassium and cesium ions affect gating charge movement and closing kinetics in voltage-gated Kv1.5 channels.
- Measured gating currents in human embryonic kidney (HEK) cells overexpressing wild-type human Kv1.5 channels and nonconducting W472F mutant channels.
- Recorded off-gating charge movements upon repolarization before and after cellular potassium dialysis, as well as in the presence of cesium ions.
- Permeating potassium or cesium ions accelerated the return of off-gating charge during repolarization compared to ion-free conditions.
- Accelerated charge return was absent in nonconducting W472F mutant channels where ion permeation was eliminated.
- Permeant cations allosterically reduce the activation energy barrier for channel closing, either via a late activation step or by retarding C-type inactivation.
Structured PICO
P
Population
Human embryonic kidney cells highly overexpressing the voltage-gated K+ channel Kv1.5 (and nonconducting mutant W472F)
I
Intervention
Presence of permeating cations (K+ or Cs+)
C
Comparator
Absence of permeant ions
O
Outcome
Off-gating current amplitudes and time coursesurrogate
Permeating cations allosterically modulate K+ channel gating currents, reducing the activation energy barrier for channel closing, which may be important during repetitive action potential spiking.
Cite This Study
Chen et al. (1997) studied this question.