1. Structural Biology and Molecular Biophysics
  2. Neuroscience
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Molecular mechanism of voltage-dependent potentiation of KCNH potassium channels

  1. William N Zagotta  Is a corresponding author
  2. Gucan Dai
  1. University of Washington, United States
Research Article
  • Cited 28
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Cite this article as: eLife 2017;6:e26355 doi: 10.7554/eLife.26355

Abstract

EAG-like (ELK) voltage-gated potassium channels are abundantly expressed in the brain. These channels exhibit a behavior called voltage-dependent potentiation (VDP), which appears to be a specialization to dampen the hyperexitability of neurons. VDP manifests as a potentiation of current amplitude, hyperpolarizing shift in voltage sensitivity, and slowing of deactivation in response to a depolarizing prepulse. Here we show that VDP of D. rerio ELK channels involves the structural interaction between the intracellular N-terminal eag domain and C-terminal CNBHD. Combining transition metal ion FRET, patch-clamp fluorometry, and incorporation of a fluorescent noncanonical amino acid, we show that there is a rearrangement in the eag domain-CNBHD interaction with the kinetics, voltage-dependence, and ATP-dependence of VDP. We propose that the activation of ELK channels involves a slow open-state dependent rearrangement of the direct interaction between the eag domain and CNBHD, which stabilized the opening of the channel.

Article and author information

Author details

  1. William N Zagotta

    Department of Physiology and Biophysics, University of Washington, Seattle, United States
    For correspondence
    zagotta@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7631-8168
  2. Gucan Dai

    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 Mental Health (R01MH102378)

  • William N Zagotta

National Eye Institute (R01EY010329)

  • William N Zagotta

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 National Institutes of Health. All of the animals were handled according to an approved institutional animal care and use committee (IACUC) protocol (#2689-01 ) of the University of Washington.

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: February 25, 2017
  2. Accepted: April 24, 2017
  3. Accepted Manuscript published: April 26, 2017 (version 1)
  4. Accepted Manuscript updated: April 27, 2017 (version 2)
  5. Version of Record published: May 22, 2017 (version 3)

Copyright

© 2017, Zagotta & Dai

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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