Voltage-dependent C-type inactivation in a constitutively open K+ channel
Gianina Panaghie1, Kerry Purtell, Kwok-Keung Tai
1Greenberg Division of Cardiology, Department of Medicine, Cornell University, Weill Medical College, New York, New York, USA.
Biophysical Journal
|June 24, 2008
Summary
Voltage-gated potassium (Kv) channels C-type inactivation is voltage-dependent. A KCNQ1 mutation (F340W) allows studying this process without voltage-dependent activation, revealing S4
Area of Science:
- Molecular Biology
- Biophysics
- Ion Channel Physiology
Background:
- Voltage-gated potassium (Kv) channels are crucial for cellular electrical signaling.
- C-type inactivation is a key gating process in Kv channels, but its voltage dependence is poorly understood.
- Concomitant voltage-dependent activation complicates mechanistic studies of C-type inactivation.
Purpose of the Study:
- To investigate the voltage dependence of C-type inactivation in Kv channels.
- To elucidate the mechanistic aspects of C-type inactivation independent of voltage-dependent activation.
- To identify key residues and domains involved in Kv channel gating and inactivation.
Main Methods:
- Site-directed mutagenesis of KCNQ1 channels (F340W mutation).
- Electrophysiological recordings (e.g., patch-clamp) to assess channel gating and inactivation.
- Analysis of inactivation kinetics, recovery, ion selectivity, and gating charge.
Main Results:
- The F340W mutation in KCNQ1 channels resulted in constitutive activation but voltage-dependent C-type inactivation.
- Inactivation was sensitive to extracellular cation concentration and altered ion selectivity, suggesting pore constriction.
- Voltage-dependent inactivation and recovery were observed, with an estimated gating charge (zi) of approximately 1.
- Double mutants confirmed the involvement of S4 in voltage-dependent C-type inactivation.
Conclusions:
- The F340W-KCNQ1 channel system allows studying voltage-dependent C-type inactivation independently of voltage-dependent activation.
- This mutation reveals a critical role for residue F340 in KCNQ1 gating and modulation by MinK.
- The findings suggest a direct coupling mechanism between C-type inactivation and S4 movement, providing a unique model for further research.
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