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@proceedings{2334064,
author = {Bébarová, Markéta and Švecová, Olga and Král, Martin and Zelenák, Štefan and Pacherník, Jiří and Bárta, Tomáš and Lietava, Samuel and Synková, Iva and Zídková, Jana and Novotný, Tomáš},
booktitle = {47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology},
keywords = {proarrhythmic stimuli; Y4734C-RYR2; idiopathic ventricular fibrillation},
language = {eng},
title = {Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation},
year = {2023}
}
TY - CONF
ID - 2334064
AU - Bébarová, Markéta - Švecová, Olga - Král, Martin - Zelenák, Štefan - Pacherník, Jiří - Bárta, Tomáš - Lietava, Samuel - Synková, Iva - Zídková, Jana - Novotný, Tomáš
PY - 2023
TI - Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation
KW - proarrhythmic stimuli
KW - Y4734C-RYR2
KW - idiopathic ventricular fibrillation
N2 - Background: The RYR2 variant Y4734C was identified in a patient suffering from idiopathic ventricular fibrillation. To investigate its pathogenic character, functional analysis has been started. Here, we present the pilot data on potential proarrhythmic stimuli in this variant. Material and Methods: The recordings of the spontaneous electrical activity of Y4734C-RYR2 (Y4734C) and unrelated healthy control (WT) hiPSC-CM (5 and 3 measured samples, respectively) were performed using the multielectrode array (MEA) technique at 37°C. Besides the evaluation of the cycle length (CL), the short-term variability of CL (STVCL) was calculated. Since some data were not normally distributed, the median ± interquartile range (IQR) and non-parametric statistical tests were used. Results: In the control Tyrode solution (5 mM K+ Tyr), CL significantly differed in WT and Y4734C (1.36±0.22 and 0.53±0.14 s, respectively; P 0.05), but STVCL was the same (8.0 ms). Subsequently, the possible proarrhythmic impact of additively applied hypokalaemia (3 mM K+), β-adrenergic stimulation (1 µM isoprenaline), and high temperature (40°C) was tested. In Y4734C, STVCL slightly decreased in 3 mM K+ and then gradually increased when 1 µM isoprenaline was added, first alone and later in combination with 40°C (4.1, 22.4, and 39.3 ms, respectively; P 0.05). In contrast, STVCL in WT was considerably higher only in the concurrent presence of 3 mM K+ and 1 µM isoprenaline (30.7 ms vs. 13.3 ms in 3 mM K+ and 9.3 ms in the presence of all the stimuli; P 0.05). Conclusions: The pilot data showed non-significant differences between the effect of three selected proarrhythmic stimuli, namely hypokalaemia, β-adrenergic stimulation, and high temperature, on the spontaneous electrical activity of WT- and Y4734C-RYR2 hiPSC-CM.
ER -
BÉBAROVÁ, Markéta, Olga ŠVECOVÁ, Martin KRÁL, Štefan ZELENÁK, Jiří PACHERNÍK, Tomáš BÁRTA, Samuel LIETAVA, Iva SYNKOVÁ, Jana ZÍDKOVÁ a Tomáš NOVOTNÝ. Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation. In \textit{47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology}. 2023.
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