Polyunsaturated fatty acid analogues differentially affect cardiac nav, cav, and kv channels through unique mechanisms

Briana M. Bohannon, Alicia de la Cruz, Xiaoan Wu, Jessica J. Jowais, Marta E. Perez, Sara I. Liin, H. Peter Larsson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere51453
JournaleLife
Volume9
DOIs
StatePublished - Mar 2020

Keywords

  • Cav1.2
  • IKs
  • Long QT Syndrome
  • Nav1.5
  • Polyunsaturated fatty acids

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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