Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels

  1. Shawn M Lamothe
  2. Nazlee Sharmin
  3. Grace Silver
  4. Motoyasu Satou
  5. Yubin Hao
  6. Toru Tateno
  7. Victoria A Baronas
  8. Harley Takatsuna Kurata  Is a corresponding author
  1. University of Alberta, Canada
  2. 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

  1. Shawn M Lamothe

    Pharmacology, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Nazlee Sharmin

    Dentistry, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Grace Silver

    Pharmacology, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Motoyasu Satou

    Biochemistry, Dokkyo Medical University School of Medicine, Soka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Yubin Hao

    Pharmacology, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Toru Tateno

    Medicine, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Victoria A Baronas

    Pharmacology, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Harley Takatsuna Kurata

    Pharmacology/Alberta Diabetes Institute, University of Alberta, Edmonton, Canada
    For correspondence
    kurata@ualberta.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4357-4189

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

  1. Baron Chanda, Washington University in St. Louis, United States

Version history

  1. Received: January 6, 2020
  2. Accepted: November 6, 2020
  3. Accepted Manuscript published: November 9, 2020 (version 1)
  4. 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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  1. Shawn M Lamothe
  2. Nazlee Sharmin
  3. Grace Silver
  4. Motoyasu Satou
  5. Yubin Hao
  6. Toru Tateno
  7. Victoria A Baronas
  8. Harley Takatsuna Kurata
(2020)
Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels
eLife 9:e54916.
https://doi.org/10.7554/eLife.54916

Share this article

https://doi.org/10.7554/eLife.54916

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