Polyunsaturated fatty acid analogues differentially affect cardiac Na<sub>V</sub>, Ca<sub>V</sub>, and K<sub>V</sub> channels through unique mechanisms.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32207683.
- Also identified by DOI 10.7554/eLife.51453 and PMC identifier 7159882.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The cardiac ventricular action potential depends on several voltage-gated ion channels, including Na<sub>V</sub>, Ca<sub>V</sub>, and K<sub>V</sub> 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 (Na<sub>V</sub>, Ca<sub>V</sub>, and K<sub>V</sub>). In addition, a PUFA analogue selective for the cardiac I<sub>Ks</sub> 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.
Medical subject headings
- Calcium Channels, L-Type
- Fatty Acids, Unsaturated
- KCNQ1 Potassium Channel
- NAV1.5 Voltage-Gated Sodium Channel
- Potassium Channels, Voltage-Gated
- Xenopus Proteins