Polyunsaturated fatty acid analogues differentially affect cardiac Nav, Cav, and Kv channels through unique mechanisms

  1. Briana M Bohannon
  2. Alicia de la Cruz
  3. Xiaoan Wu
  4. Jessica J Jowais
  5. Marta E Perez
  6. Sara I Liin
  7. H Peter Larsson  Is a corresponding author
  1. University of Miami, United States
  2. Linköping University, Sweden

Abstract

The cardiac ventricular action potential depends on several voltage-gated ion channels, including Nav, Cav, and Kv channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels. Here we demonstrate that PUFA analogues vary in their selectivity for human voltage-gated ion channels involved in the ventricular action potential. The effects of specific PUFA analogues range from selective for a specific ion channel to broadly modulating cardiac ion channels from all three families (Nav, Cav, and KV). In addition, a PUFA analogue selective for the cardiac IKs channel (Kv7.1/KCNE1) is effective in shortening the cardiac action potential in human-induced pluripotent stem cell-derived cardiomyocytes. Our data suggest that PUFA analogues could potentially be developed as therapeutics for LQTS and cardiac arrhythmia.

Data availability

Source data used in this manuscript is openly available and is listed as a source data file for accessibility.

Article and author information

Author details

  1. Briana M Bohannon

    Physiology and Biophysics, University of Miami, Miami, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3720-1477
  2. Alicia de la Cruz

    Physiology and Biophysics, University of Miami, Miami, United States
    Competing interests
    No competing interests declared.
  3. Xiaoan Wu

    Physiology and Biophysics, University of Miami, Miami, United States
    Competing interests
    No competing interests declared.
  4. Jessica J Jowais

    Physiology and Biophysics, University of Miami, Miami, United States
    Competing interests
    No competing interests declared.
  5. Marta E Perez

    Physiology and Biophysics, University of Miami, Miami, United States
    Competing interests
    No competing interests declared.
  6. Sara I Liin

    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
    Competing interests
    Sara I Liin, A patent application (62/032,739) has been submitted by the University of Miami with SIL and HPL as inventors. The authors declare no other competing interests.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8493-0114
  7. H Peter Larsson

    Department of Physiology and Biophysics, University of Miami, Miami, United States
    For correspondence
    plarsson@med.miami.edu
    Competing interests
    H Peter Larsson, A patent application (62/032,739) has been submitted by the University of Miami with SIL and HPL as inventors. The authors declare no other competing interests.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1688-2525

Funding

National Institutes of Health (R01-HL131461)

  • H Peter Larsson

Swedish Research Council (2017-02040)

  • Sara I Liin

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

Reviewing Editor

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

Publication history

  1. Received: August 29, 2019
  2. Accepted: March 24, 2020
  3. Accepted Manuscript published: March 24, 2020 (version 1)
  4. Version of Record published: April 15, 2020 (version 2)
  5. Version of Record updated: June 18, 2020 (version 3)

Copyright

© 2020, Bohannon 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. Briana M Bohannon
  2. Alicia de la Cruz
  3. Xiaoan Wu
  4. Jessica J Jowais
  5. Marta E Perez
  6. Sara I Liin
  7. H Peter Larsson
(2020)
Polyunsaturated fatty acid analogues differentially affect cardiac Nav, Cav, and Kv channels through unique mechanisms
eLife 9:e51453.
https://doi.org/10.7554/eLife.51453

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