Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage

  1. Oscar Vivas  Is a corresponding author
  2. Claudia M Moreno
  3. Luis F Santana
  4. Bertil Hille
  1. University of Washington, United States
  2. University of California, Davis, United States

Abstract

CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near -50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials.

Article and author information

Author details

  1. Oscar Vivas

    Department of Physiology and Biophysics, University of Washington, Seattle, United States
    For correspondence
    vivas@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0964-385X
  2. Claudia M Moreno

    Department of Physiology and Biophysics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Luis F Santana

    Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4297-8029
  4. Bertil Hille

    Department of Physiology and Biophysics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institute of Neurological Disorders and Stroke (R37NS008174)

  • Bertil Hille

National Heart, Lung, and Blood Institute (R01HL085686)

  • Luis F Santana

Wayne E. Crill Endowed Professorship (Professor Fellowship)

  • Bertil Hille

National Heart, Lung, and Blood Institute (R01HL085870)

  • Luis F Santana

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animals were handled according to guidelines approved by the University of Washington Institutional Animal Care and Use Committee (#2084-03).

Reviewing Editor

  1. Kenton J Swartz, National Institutes of Health, United States

Publication history

  1. Received: April 23, 2017
  2. Accepted: June 28, 2017
  3. Accepted Manuscript published: June 30, 2017 (version 1)
  4. Accepted Manuscript updated: July 3, 2017 (version 2)
  5. Version of Record published: July 10, 2017 (version 3)

Copyright

© 2017, Vivas 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. Oscar Vivas
  2. Claudia M Moreno
  3. Luis F Santana
  4. Bertil Hille
(2017)
Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage
eLife 6:e28029.
https://doi.org/10.7554/eLife.28029

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