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A quantitative description of KcsA gating II: single-channel currents
Sudha Chakrapani1, Julio F Cordero-Morales, Eduardo Perozo
1Institute of Molecular Pediatrics Science, Department of Biochemistry and Molecular Biology, University of Chicago, Center for Integrative Science, Chicago, IL 60637, USA.
The Journal of General Physiology
|October 17, 2007
Summary
Protons activate KcsA ion channels by increasing burst frequency, while voltage influences burst properties and inactivation states. A new kinetic model describes these gating events.
Area of Science:
- Biophysics
- Ion Channel Physiology
Background:
- KcsA is a potassium channel crucial for cellular potassium transport.
- Understanding its gating mechanisms is key to ion channel function.
Purpose of the Study:
- To investigate the kinetic transitions of wild-type (WT) KcsA and a noninactivating mutant (E71A) at the single-channel level.
- To elucidate the roles of pH and voltage in KcsA channel gating.
Main Methods:
- Single-channel patch-clamp recordings of purified, liposome-reconstituted KcsA.
- Nonstationary and steady-state current analysis.
- Maximum-likelihood kinetic modeling.
Main Results:
- Acidic pH increases KcsA bursting frequency without altering intraburst kinetics.
- Voltage modulates burst frequency, flicker frequency, and dwell times of open/closed states.
- Voltage-dependent closed states, distinct from activation, likely represent inactivation.
- Subconductance states were observed but their modulation by pH or voltage remains unclear.
Conclusions:
- Protons primarily affect KcsA activation frequency, while voltage influences both activation and inactivation.
- A kinetic model successfully recapitulates KcsA's macroscopic and single-channel gating behavior.
- Further research is needed to clarify the origin of subconductance states.
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