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.

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.

Metrics

  • 1,175
    views
  • 151
    downloads
  • 8
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Ecology
    2. Neuroscience
    Kathleen T Quach, Gillian A Hughes, Sreekanth H Chalasani
    Research Article

    Prey must balance predator avoidance with feeding, a central dilemma in prey refuge theory. Additionally, prey must assess predatory imminence—how close threats are in space and time. Predatory imminence theory classifies defensive behaviors into three defense modes: pre-encounter, post-encounter, and circa-strike, corresponding to increasing levels of threat—–suspecting, detecting, and contacting a predator. Although predatory risk often varies in spatial distribution and imminence, how these factors intersect to influence defensive behaviors is poorly understood. Integrating these factors into a naturalistic environment enables comprehensive analysis of multiple defense modes in consistent conditions. Here, we combine prey refuge and predatory imminence theories to develop a model system of nematode defensive behaviors, with Caenorhabditis elegans as prey and Pristionchus pacificus as predator. In a foraging environment comprised of a food-rich, high-risk patch and a food-poor, low-risk refuge, C. elegans innately exhibits circa-strike behaviors. With experience, it learns post- and pre-encounter behaviors that proactively anticipate threats. These defense modes intensify with predator lethality, with only life-threatening predators capable of eliciting all three modes. SEB-3 receptors and NLP-49 peptides, key stress regulators, vary in their impact and interdependence across defense modes. Overall, our model system reveals fine-grained insights into how stress-related signaling regulates defensive behaviors.

    1. Neuroscience
    Markus R Tünte, Stefanie Hoehl ... Ezgi Kayhan
    Research Advance

    Several recent theoretical accounts have posited that interoception, the perception of internal bodily signals, plays a vital role in early human development. Yet, empirical evidence of cardiac interoceptive sensitivity in infants to date has been mixed. Furthermore, existing evidence does not go beyond the perception of cardiac signals and focuses only on the age of 5–7 mo, limiting the generalizability of the results. Here, we used a modified version of the cardiac interoceptive sensitivity paradigm introduced by Maister et al., 2017 in 3-, 9-, and 18-mo-old infants using cross-sectional and longitudinal approaches. Going beyond, we introduce a novel experimental paradigm, namely the iBREATH, to investigate respiratory interoceptive sensitivity in infants. Overall, for cardiac interoceptive sensitivity (total n=135) we find rather stable evidence across ages with infants on average preferring stimuli presented synchronously to their heartbeat. For respiratory interoceptive sensitivity (total n=120) our results show a similar pattern in the first year of life, but not at 18 mo. We did not observe a strong relationship between cardiac and respiratory interoceptive sensitivity at 3 and 9 mo but found some evidence for a relationship at 18 mo. We validated our results using specification curve- and mega-analytic approaches. By examining early cardiac and respiratory interoceptive processing, we provide evidence that infants are sensitive to their interoceptive signals.