Dynamic change of electrostatic field in TMEM16F permeation pathway shifts its ion selectivity

  1. Wenlei Ye
  2. Tina W Han
  3. Mu He
  4. Yuh Nung Jan
  5. Lily Yeh Jan  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, San Francisco, United States

Abstract

TMEM16F is activated by elevated intracellular Ca2+, and functions as a small-conductance ion channel and as a phospholipid scramblase. In contrast to its paralogs, the TMEM16A/B calcium-activated chloride channels, mouse TMEM16F has been reported as a cation-, anion-, or non-selective ion channel, without a definite conclusion. Starting with the Q559K mutant that shows no current rundown and less outward rectification in excised patch, we found that the channel shifted its ion selectivity in response to the change of intracellular Ca2+ concentration, with an increased permeability ratio of Cl- to Na+ (PCl-/PNa+) at a higher Ca2+ level. The gradual shift of relative ion permeability did not correlate with the channel activation state. Instead, it was indicative of an alteration of electrostatic field in the permeation pathway. The dynamic change of ion selectivity suggests a charge-screening mechanism for TMEM16F ion conduction, and it provides hints to the study of TMEM16F physiological functions.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Wenlei Ye

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4694-1493
  2. Tina W Han

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mu He

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuh Nung Jan

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1367-6299
  5. Lily Yeh Jan

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    For correspondence
    Lily.Jan@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3938-8498

Funding

National Institute of Neurological Disorders and Stroke (R01NS069229)

  • Lily Yeh Jan

Jane Coffin Childs Memorial Fund for Medical Research

  • Tina W Han

Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD089639)

  • Mu He

Howard Hughes Medical Institute

  • Yuh Nung Jan
  • Lily Yeh Jan

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

Reviewing Editor

  1. Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Publication history

  1. Received: January 14, 2019
  2. Accepted: July 17, 2019
  3. Accepted Manuscript published: July 18, 2019 (version 1)
  4. Version of Record published: August 12, 2019 (version 2)

Copyright

© 2019, Ye 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. Wenlei Ye
  2. Tina W Han
  3. Mu He
  4. Yuh Nung Jan
  5. Lily Yeh Jan
(2019)
Dynamic change of electrostatic field in TMEM16F permeation pathway shifts its ion selectivity
eLife 8:e45187.
https://doi.org/10.7554/eLife.45187

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