1. Neuroscience
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The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision

  1. Frans Vinberg
  2. Tian Wang
  3. Alicia De Maria
  4. Haiqing Zhao
  5. Steven Bassnett
  6. Jeannie Chen  Is a corresponding author
  7. Vladimir J Kefalov  Is a corresponding author
  1. Washington University in St. Louis, United States
  2. Keck School of Medicine, University of Southern California, United States
  3. Johns Hopkins University, United States
Research Article
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Cite this article as: eLife 2017;6:e24550 doi: 10.7554/eLife.24550

Abstract

Calcium (Ca2+) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na+/Ca2+, K+ exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2: NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival.

Article and author information

Author details

  1. Frans Vinberg

    Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tian Wang

    Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alicia De Maria

    Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Haiqing Zhao

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Steven Bassnett

    Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jeannie Chen

    Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, United States
    For correspondence
    jeannie@med.usc.edu
    Competing interests
    The authors declare that no competing interests exist.
  7. Vladimir J Kefalov

    Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, United States
    For correspondence
    Kefalov@vision.wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1659-008X

Funding

National Eye Institute (EY019312 EY025696 EY012155 EY026651)

  • Frans Vinberg
  • Tian Wang
  • Alicia De Maria
  • Steven Bassnett
  • Jeannie Chen
  • Vladimir J Kefalov

Research to Prevent Blindness

  • Frans Vinberg
  • Alicia De Maria
  • Steven Bassnett
  • Vladimir J Kefalov

Ella ja Georg Ehrnroothin Säätiö

  • Frans Vinberg

National Institute on Deafness and Other Communication Disorders (DC007395)

  • Haiqing Zhao

National Eye Institute (EY027387)

  • Jeannie Chen
  • Vladimir J Kefalov

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 approved institutional animal care and use committee (IACUC) protocols (#A-3381-01) of the University of Washington in St. Louis..

Reviewing Editor

  1. Fred Rieke, Howard Hughes Medical Institute, University of Washington, United States

Publication history

  1. Received: December 22, 2016
  2. Accepted: June 23, 2017
  3. Accepted Manuscript published: June 26, 2017 (version 1)
  4. Version of Record published: July 18, 2017 (version 2)

Copyright

© 2017, Vinberg 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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