Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels
- University of Alberta, Canada
- Dokkyo Medical University School of Medicine, Japan
Abstract
Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement ('disinhibition') with holding potentials more negative than -120 mV. Knockdown of endogenous Slc7a5 leads to larger Kv1.1 currents, and strongly attenuates the disinhibition effect, suggesting that Slc7a5 regulation of Kv1.1 involves channel inhibition that can be reversed by supraphysiological hyperpolarizing voltages. We investigated chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5, and localize a specific position in S1 with prominent effects on Slc7a5 sensitivity. Overall, our study highlights multiple Slc7a5-sensitive Kv1 subunits, and identifies the voltage-sensing domain as a determinant of Slc7a5 modulation of Kv1 channels.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.
Article and author information
Author details
Harley Takatsuna Kurata
Funding
Canadian Institutes of Health Research (Project Grant)
- Harley Takatsuna Kurata
Canadian Institutes of Health Research (Vanier Studentship)
- Victoria A Baronas
University of Alberta (Rowland and Muriel Haryett fellowship)
- Shawn M Lamothe
Natural Sciences and Engineering Research Council of Canada (USRA)
- Grace Silver
Canadian Institutes of Health Research (Early Career Investigator)
- Harley Takatsuna Kurata
Alberta Diabetes Institute (Salary support)
- Harley Takatsuna Kurata
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Baron Chanda, Washington University in St. Louis, United States
Version history
- Received: January 6, 2020
- Accepted: November 6, 2020
- Accepted Manuscript published: November 9, 2020 (version 1)
- Version of Record published: November 26, 2020 (version 2)
Copyright
© 2020, Lamothe 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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Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels
eLife 9:e54916.
https://doi.org/10.7554/eLife.54916
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