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.

Základní údaje

Originální název

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

Autoři

KRÁL, Martin (203 Česká republika, domácí), Olga ŠVECOVÁ (203 Česká republika, domácí), Štefan ZELENÁK (703 Slovensko), Jiří PACHERNÍK (203 Česká republika), Tomáš BÁRTA (203 Česká republika, domácí), Jana ZÍDKOVÁ (203 Česká republika, domácí), Iva SYNKOVÁ (203 Česká republika, domácí), Samuel LIETAVA (703 Slovensko, domácí), Tomáš NOVOTNÝ (203 Česká republika, domácí) a Markéta BÉBAROVÁ (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Rakousko

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

RYR2; Y4734C; multielectrode array; electrical activity; isoprenaline

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 19. 8. 2024 14:14, Mgr. Tereza Miškechová

Anotace

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.

Návaznosti

MUNI/A/1547/2023, interní kód MU

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

Investor: Masarykova univerzita, Analýza (dys)funkce: od molekul k živému organismu

NU22-02-00348, projekt VaV

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

Investor: Ministerstvo zdravotnictví ČR, Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus, Podprogram 1 - standardní

Citovat

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 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 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.

Podrobný výpis o publikaci