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@proceedings{2417419,
author = {Král, Martin and Švecová, Olga and Zelenák, Štefan and Pacherník, Jiří and Bárta, Tomáš and Zídková, Jana and Synková, Iva and Lietava, Samuel and Novotný, Tomáš and Bébarová, Markéta},
booktitle = {48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology},
keywords = {RYR2, Y4734C, multielectrode array, electrical activity, isoprenaline},
language = {eng},
title = {Effect of isoprenaline and arrhythmogenic conditions on the spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2 variant},
year = {2024}
}
TY - CONF
ID - 2417419
AU - Král, Martin - Švecová, Olga - Zelenák, Štefan - Pacherník, Jiří - Bárta, Tomáš - Zídková, Jana - Synková, Iva - Lietava, Samuel - Novotný, Tomáš - Bébarová, Markéta
PY - 2024
TI - Effect of isoprenaline and arrhythmogenic conditions on the spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2 variant
KW - RYR2, Y4734C, multielectrode array, electrical activity, isoprenaline
N2 - Background: In a proband with idiopathic ventricular fibrillation (IF) and in his sister suffering from catecholaminergic polymorphic ventricular tachycardia (CPVT), p.Y4734C-RYR2 variant was found. Here we bring data showing the spontaneous electrical activity of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) of the proband (IF), his sister (CPVT), and his healthy nephew as control (WT), and its changes under arrhythmogenic conditions. Methods: The recordings by the multielectrode array technique were performed in control, i.e. in Tyrode solution with 5 mM K+ (5K++37°C), in 0.5 µM isoprenaline (ISO), and under cumulatively added hypokalemia (3K+), β-adrenergic stimulation (ISO), and hyperthermia (40°C). Considering non-normal data distribution, the cycle length (CL) and its short-term variability (STVCL) are shown as the median from n samples and non-parametric tests were used. Results: In 5K+, CPVT hiPSC-CM had a significantly longer CL (1.47 s, n=19; P˂0.05) than IF (1.05 s, n=32) and WT (0.77 s, n=7). ISO significantly shortened CL in all groups (by 38.3, 22.7, and 17.7 % in CPVT, IF, and WT, respectively, n=19, 32, and 7; P ˂ 0.05) and CPVT showed a significantly larger reaction than IF (P˂0.05). The arrhythmogenic factors caused a significant increment in STVCL in IF (41.91 in 3K+, 22.65 in 3K++ISO, and 65.38 ms in 3K++ISO+40°C, vs. 10.23 ms in control; n=24; P˂0.05) whereas it was significantly increased only in 3K+ in CPVT (21.14, 15.99, and 10.44 ms, respectively, vs. 13.13 in control; n=20; P˂0.05). IF and CPVT significantly differed in STVCL in 3K++ISO+40°C. Conclusions: CPVT hiPSC-CM showed a lower frequency of spontaneous activity and its higher reactivity to ISO. An increment in beat-to-beat variability of CL was observed during arrhythmogenic conditions in IF hiPSC-CM.
ER -
KRÁL, Martin, Olga ŠVECOVÁ, Štefan ZELENÁK, Jiří PACHERNÍK, Tomáš BÁRTA, Jana ZÍDKOVÁ, Iva SYNKOVÁ, Samuel LIETAVA, Tomáš NOVOTNÝ a Markéta BÉBAROVÁ. Effect of isoprenaline and arrhythmogenic conditions on the spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2 variant. In \textit{48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology}. 2024.
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