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

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..

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.

Metrics

  • 2,008
    views
  • 256
    downloads
  • 35
    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. Frans Vinberg
  2. Tian Wang
  3. Alicia De Maria
  4. Haiqing Zhao
  5. Steven Bassnett
  6. Jeannie Chen
  7. Vladimir J Kefalov
(2017)
The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision
eLife 6:e24550.
https://doi.org/10.7554/eLife.24550

Share this article

https://doi.org/10.7554/eLife.24550

Further reading

    1. Neuroscience
    Xinlin Hou, Peng Zhang ... Dandan Zhang
    Research Article

    Emotional responsiveness in neonates, particularly their ability to discern vocal emotions, plays an evolutionarily adaptive role in human communication and adaptive behaviors. The developmental trajectory of emotional sensitivity in neonates is crucial for understanding the foundations of early social-emotional functioning. However, the precise onset of this sensitivity and its relationship with gestational age (GA) remain subjects of investigation. In a study involving 120 healthy neonates categorized into six groups based on their GA (ranging from 35 and 40 weeks), we explored their emotional responses to vocal stimuli. These stimuli encompassed disyllables with happy and neutral prosodies, alongside acoustically matched nonvocal control sounds. The assessments occurred during natural sleep states using the odd-ball paradigm and event-related potentials. The results reveal a distinct developmental change at 37 weeks GA, marking the point at which neonates exhibit heightened perceptual acuity for emotional vocal expressions. This newfound ability is substantiated by the presence of the mismatch response, akin to an initial form of adult mismatch negativity, elicited in response to positive emotional vocal prosody. Notably, this perceptual shift’s specificity becomes evident when no such discrimination is observed in acoustically matched control sounds. Neonates born before 37 weeks GA do not display this level of discrimination ability. This developmental change has important implications for our understanding of early social-emotional development, highlighting the role of gestational age in shaping early perceptual abilities. Moreover, while these findings introduce the potential for a valuable screening tool for conditions like autism, characterized by atypical social-emotional functions, it is important to note that the current data are not yet robust enough to fully support this application. This study makes a substantial contribution to the broader field of developmental neuroscience and holds promise for future research on early intervention in neurodevelopmental disorders.

    1. Neuroscience
    Luis Alberto Bezares Calderón, Réza Shahidi, Gáspár Jékely
    Research Article

    Hydrostatic pressure is a dominant environmental cue for vertically migrating marine organisms but the physiological mechanisms of responding to pressure changes remain unclear. Here, we uncovered the cellular and circuit bases of a barokinetic response in the planktonic larva of the marine annelid Platynereis dumerilii. Increased pressure induced a rapid, graded, and adapting upward swimming response due to the faster beating of cilia in the head multiciliary band. By calcium imaging, we found that brain ciliary photoreceptors showed a graded response to pressure changes. The photoreceptors in animals mutant for ciliary opsin-1 had a smaller sensory compartment and mutant larvae showed diminished pressure responses. The ciliary photoreceptors synaptically connect to the head multiciliary band via serotonergic motoneurons. Genetic inhibition of the serotonergic cells blocked pressure-dependent increases in ciliary beating. We conclude that ciliary photoreceptors function as pressure sensors and activate ciliary beating through serotonergic signalling during barokinesis.