Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms

eLife

Sara I Liin¹  Briana M Bohannon²  Xiaoan Wu²  Marta E Perez²  H Peter Larsson²  Alicia de la Cruz²  Jessica J Jowais² 

[1] Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden;Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, United States;

关键词: Xenopus;    iks;    Cav1.2;    Nav1.5;    Long QT Syndrome;    polyunsaturated fatty acids;    None;   

DOI  :  10.7554/eLife.51453

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY