Effect of helical kink in antimicrobial peptides on membrane pore formation

0523363 - ÚFCH JH 2021 RIV GB eng J - Journal Article
Tuerková, A. - Kabelka, I. - Králová, T. - Sukeník, L. - Pokorná, Šárka - Hof, Martin - Vácha, R.
Effect of helical kink in antimicrobial peptides on membrane pore formation.
eLife. Roč. 9, FEB 2020 (2020), č. článku 47946. ISSN 2050-084X. E-ISSN 2050-084X
R&D Projects: GA ČR(CZ) GX19-26854X
Grant - others:Ga MŠk(CZ) LM2015070; GA MŠk(CZ) LM2015042; GA MŠk(CZ) LM2015085
Institutional support: RVO:61388955
Keywords : antimicrobial peptides * membranes * fluorescence
OECD category: Physical chemistry
Impact factor: 8.146, year: 2020
Method of publishing: Open access

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.
Permanent Link: http://hdl.handle.net/11104/0307723