Effect of isoprenaline and arrhythmogenic conditions on the
spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2
variant

a 2024

Effect of isoprenaline and arrhythmogenic conditions on the spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2 variant

KRÁL, Martin, Olga ŠVECOVÁ, Štefan ZELENÁK, Jiří PACHERNÍK, Tomáš BÁRTA et. al.

Basic information

Original name

Effect of isoprenaline and arrhythmogenic conditions on the spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2 variant

Authors

KRÁL, Martin (203 Czech Republic, belonging to the institution), Olga ŠVECOVÁ (203 Czech Republic, belonging to the institution), Štefan ZELENÁK (703 Slovakia), Jiří PACHERNÍK (203 Czech Republic), Tomáš BÁRTA (203 Czech Republic, belonging to the institution), Jana ZÍDKOVÁ (203 Czech Republic, belonging to the institution), Iva SYNKOVÁ (203 Czech Republic, belonging to the institution), Samuel LIETAVA (703 Slovakia, belonging to the institution), Tomáš NOVOTNÝ (203 Czech Republic, belonging to the institution) and Markéta BÉBAROVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2024

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Austria

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

Keywords in English

RYR2; Y4734C; multielectrode array; electrical activity; isoprenaline

Abstract

V originále

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.

Links

MUNI/A/1547/2023, interní kód MU

Name: Analýza (dys)funkce: od molekul k živému organismu

Investor: Masaryk University, Analysis of (dys)function: from molecules to the living organism

NU22-02-00348, research and development project

Name: Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Citovat

KRÁL, Martin, Olga ŠVECOVÁ, Štefan ZELENÁK, Jiří PACHERNÍK, Tomáš BÁRTA, Jana ZÍDKOVÁ, Iva SYNKOVÁ, Samuel LIETAVA, Tomáš NOVOTNÝ and Markéta BÉBAROVÁ. Effect of isoprenaline and arrhythmogenic conditions on the spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2 variant. In 48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology. 2024.

@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
KW  - Y4734C
KW  - multielectrode array
KW  - electrical activity
KW  - 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 and 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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