TRPV4 is the temperature-sensitive ion channel of human sperm

  1. Nadine Mundt
  2. Marc Spehr
  3. Polina V Lishko  Is a corresponding author
  1. University of California, Berkeley, United States
  2. RWTH Aachen University, Germany

Abstract

Ion channels control human sperm fertilizing ability by triggering hyperactivated motility, which is regulated by membrane potential, intracellular pH, and cytosolic calcium. Previous studies unraveled three essential ion channels that regulate these parameters: 1) the Ca2+ channel CatSper, 2) the K+ channel KSper, and 3) the H+ channel Hv1. However, the molecular identity of the sperm Na+ conductance that mediates initial membrane depolarization and, thus, triggers downstream signaling events is yet to be defined. Here, we functionally characterize DSper, the Depolarizing Channel of Sperm, as the temperature-activated channel TRPV4. It is functionally expressed at both mRNA and protein levels, while other temperature-sensitive TRPV channels are not functional in human sperm. DSper currents are activated by warm temperatures and mediate cation conductance, that shares a pharmacological profile reminiscent of TRPV4. Together, these results suggest that TRPV4 activation triggers initial membrane depolarization, facilitating both CatSper and Hv1 gating and, consequently, sperm hyperactivation.

Data availability

All data generated or analyzed 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. Nadine Mundt

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marc Spehr

    Department of Chemosensation, Institute for Biology II, RWTH Aachen University, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6616-4196
  3. Polina V Lishko

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    lishko@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3140-2769

Funding

National Institute of General Medical Sciences (R01GM111802)

  • Polina V Lishko

Pew Charitable Trusts (28642)

  • Polina V Lishko

Alfred P. Sloan Foundation (FR‐2015‐65398)

  • Polina V Lishko

Deutscher Akademischer Austauschdienst

  • Nadine Mundt

Packer Wentz Endowment Will

  • Polina V Lishko

Rose Hill Innovator Fund

  • Polina V Lishko

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

Ethics

Human subjects: The participation of healthy human sperm donor volunteers was approved by the Committee on Human Research at the University of California, Berkeley (protocol number 2013-06-5395). All donors provided informed consent.

Reviewing Editor

  1. Leon D Islas, Universidad Nacional Autónoma de México, Mexico

Publication history

  1. Received: February 11, 2018
  2. Accepted: June 30, 2018
  3. Accepted Manuscript published: July 2, 2018 (version 1)
  4. Accepted Manuscript updated: July 4, 2018 (version 2)
  5. Version of Record published: July 18, 2018 (version 3)

Copyright

© 2018, Mundt 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. Nadine Mundt
  2. Marc Spehr
  3. Polina V Lishko
(2018)
TRPV4 is the temperature-sensitive ion channel of human sperm
eLife 7:e35853.
https://doi.org/10.7554/eLife.35853
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