Calcium-driven regulation of voltage-sensing domains in BK channels
- Universidad de Valparaíso, Chile
Abstract
Allosteric interactions between the voltage-sensing domain (VSD), the Ca2+-binding sites, and the pore domain govern the mammalian Ca2+- and voltage-activated K+ (BK) channel opening. However, the functional relevance of the crosstalk between the Ca2+- and voltage-sensing mechanisms on BK channel gating is still debated. We examined the energetic interaction between Ca2+ binding and VSD activation by investigating the effects of internal Ca2+ on BK channel gating currents. Our results indicate that Ca2+ sensor occupancy has a strong impact on VSD activation through a coordinated interaction mechanism in which Ca2+ binding to a single α-subunit affects all VSDs equally. Moreover, the two distinct high-affinity Ca2+-binding sites contained in the C-terminus domains, RCK1 and RCK2, contribute equally to decrease the free energy necessary to activate the VSD. We conclude that voltage-dependent gating and pore opening in BK channels is modulated to a great extent by the interaction between Ca2+ sensors and VSDs.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Yenisleidy Lorenzo-Ceballos
Funding
AFOSR (No. FA9550-16-1-0384)
- Ramon Latorre
FONDECYT (Grant No. 1180999)
- Karen Castillo
CONICYT-PFCHA (Doctoral fellowship No. 63140149)
- Yenisleidy Lorenzo-Ceballos
Millennium Scientific Initiative of the Chilean Ministry of Economy, Development, and Tourism (P029-022-F)
- Yenisleidy Lorenzo-Ceballos
- Willy Carrasquel-Ursulaez
- Karen Castillo
- Osvaldo Alvarez
- Ramon Latorre
FONDECYT (Grant No. 1150273)
- Ramon Latorre
FONDECYT (Grant No. 1190203)
- Ramon Latorre
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Ethics Committee for Animal Experimentation of the University of Valparaíso. All of the animals were handled according to approved institutional animal care and use committee protocols (BEA031-14) of the University of Valparaiso. All surgery was performed under tricaine anesthesia, and every effort was made to minimize suffering.
Copyright
© 2019, Lorenzo-Ceballos et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Calcium-driven regulation of voltage-sensing domains in BK channels
eLife 8:e44934.
https://doi.org/10.7554/eLife.44934
