ORCiD
0000-0002-6489-4651
Document Type
Article
Publication Title
The Journal of General Physiology
ISSN
1540-7748
Volume
140
Issue
5
DOI
10.1085/jgp.201210817
First Page
481
Last Page
493
Publication Date
11-1-2012
Abstract
Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the subsequent membrane repolarization. Measurements of deactivating gating currents (reporting VSD movement) and ionic currents (BC gate status) showed that the kinetics of both slowed down in two distinct phases with increasing duration of the depolarizing prepulse. The biphasic slowing in VSD deactivation and BC gate closure was strongly correlated in time and magnitude. Simultaneous recordings of ionic currents and fluorescence from a probe tracking VSD movement in Shaker directly demonstrated that both processes were synchronized. Whereas the first slowing originates from a stabilization imposed by BC gate opening, the subsequent slowing reflects the rearrangement of the VSD toward its relaxed state (relaxation). The VSD relaxation was observed in the Ciona intestinalis voltage-sensitive phosphatase and in its isolated VSD. Collectively, our results show that the VSD relaxation is not kinetically related to C-type inactivation and is an intrinsic property of the VSD. We propose VSD relaxation as a general mechanism for depolarization-induced slowing of BC gate closure that may enable Kv1.2 channels to modulate the firing frequency of neurons based on the depolarization history.
Recommended Citation
Labro, A. J.,
Lacroix, J. J.,
Villalba-Galea, C. A.,
Snyders, D. J.,
&
Bezanilla, F.
(2012).
Molecular mechanism for depolarization-induced modulation of Kv channel closure.
The Journal of General Physiology, 140(5), 481–493.
DOI: 10.1085/jgp.201210817
https://scholarlycommons.pacific.edu/phs-facarticles/314
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
- Citations
- Citation Indexes: 36
- Usage
- Downloads: 115
- Abstract Views: 4
- Captures
- Readers: 50
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Chemicals and Drugs Commons, Pharmacy and Pharmaceutical Sciences Commons
Comments
Authors retain copyright