Spontaneous electrical activity of cardiomyocytes derived from
hiPSCs of a patient with idiopathic ventricular fibrillation
and RYR2 variant: impact of isoprenaline and varying
concentrations of Ca2+

a 2023

Spontaneous electrical activity of cardiomyocytes derived from hiPSCs of a patient with idiopathic ventricular fibrillation and RYR2 variant: impact of isoprenaline and varying concentrations of Ca2+

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

Základní údaje

Originální název

Spontaneous electrical activity of cardiomyocytes derived from hiPSCs of a patient with idiopathic ventricular fibrillation and RYR2 variant: impact of isoprenaline and varying concentrations of Ca2+

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), Samuel LIETAVA (703 Slovensko), Iva SYNKOVÁ (203 Česká republika), Jana ZÍDKOVÁ (203 Česká republika), Tomáš NOVOTNÝ (203 Česká republika) a Markéta BÉBAROVÁ (203 Česká republika, garant, domácí)

Vydání

47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2023, 2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Dánsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Abstract book

Kód RIV

RIV/00216224:14110/23:00132099

Organizační jednotka

Lékařská fakulta

Klíčová slova česky

RYR2; idiopatická komorová fibrilace; dědičné arytmie; hiPSC; MEA;

Klíčová slova anglicky

RYR2; idiopathic ventricular fibrillation; inhereted arrhythmia; hiPSC; MEA

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 11. 2023 12:05, Mgr. Martin Král

Anotace

V originále

Background: We have found a potentially proarrhythmic variant p. Y4734C in the ryanodine receptor type 2 (RYR2) in a patient suffering from idiopathic ventricular fibrillation. Here we bring pilot data showing the effect of 0.1 µM isoprenaline (ISO) and 0.5-5 mM Ca2+ on the spontaneous electrical activity of patient-specific cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM). Material and Methods: The spontaneous electrical activity of Y4734C-RYR2 hiPSC-CM (Y4734C) and hiPSC-CM of unrelated healthy control (WT) was recorded using the multielectrode array (MEA) technique at 37 °C. The cycle length (CL) and field potential duration (FPD and FPDc – correction according to Fridericia) are presented as the median ± interquartile range (IQR); non-parametric tests were used for comparison. Results: In control conditions (1.8 mM Ca2+), CL was insignificantly longer in WT (5.36±5.87 s; n=9) than in Y4734C (1.22±0.82 s; n=6). FDP and FPDc were significantly longer in WT (0.35±0.51 and 0.16±0.13 s, respectively; n=9) than in Y4734C (0.08±0.04 and 0.09±0.05 s, respectively; n=6; P˂0.05). Under the effect of 0.1 µM ISO, CL was shortened by 45.0±16.7% (n=9, P˂0.05) in WT and a similar, but insignificant change was observed in Y4734C (by 24.9±29.6%, n=5). We detected a significant CL prolongation in the presence of 1, 2, 3, and 5 mM Ca2+ in WT (P˂0.05) whereas it was not significantly changed in Y4734C. No significant changes in FPD and FPDc were observed both in ISO and varying concentrations of Ca2+ except for a shortened FPD in 0.1 µM ISO in WT. Conclusions: The pilot data showed longer FPD and FPDc in WT vs. Y4734C and significant changes mostly in CL in WT at 0.1 µM ISO and various Ca2+ concentrations.

Návaznosti

MUNI/A/1343/2022, interní kód MU

Název: Zátěže kardiovaskulárního systému od A po Z

Investor: Masarykova univerzita, Zátěže kardiovaskulárního systému od A po Z

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, Samuel LIETAVA, Iva SYNKOVÁ, Jana ZÍDKOVÁ, Tomáš NOVOTNÝ a Markéta BÉBAROVÁ. Spontaneous electrical activity of cardiomyocytes derived from hiPSCs of a patient with idiopathic ventricular fibrillation and RYR2 variant: impact of isoprenaline and varying concentrations of Ca2+. In 47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2023. 2023.

@proceedings{2333417,
   author = {Král, Martin and Švecová, Olga and Zelenák, Štefan and Pacherník, Jiří and Bárta, Tomáš and Lietava, Samuel and Synková, Iva and Zídková, Jana and Novotný, Tomáš and Bébarová, Markéta},
   booktitle = {47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2023},
   keywords = {RYR2; idiopathic ventricular fibrillation; inhereted arrhythmia; hiPSC; MEA},
   language = {eng},
   title = {Spontaneous electrical activity of cardiomyocytes derived from hiPSCs of a patient with idiopathic ventricular fibrillation and RYR2 variant: impact of isoprenaline and varying concentrations of Ca2+},
   url = {https://escardio.sharepoint.com/sites/ESCEvents/Shared%20Documents/Forms/AllItems.aspx?id=%2Fsites%2FESCEvents%2FShared%20Documents%2FPublic%20shared%20documents%2FWorking%20group%20Events%2F2023%2FEWGCCE%20Meeting%202023%2FEWGCCE%5F2023%5Fabstract%5Fboo},
   year = {2023}
}

TY  - CONF
ID  - 2333417
AU  - Král, Martin - Švecová, Olga - Zelenák, Štefan - Pacherník, Jiří - Bárta, Tomáš - Lietava, Samuel - Synková, Iva - Zídková, Jana - Novotný, Tomáš - Bébarová, Markéta
PY  - 2023
TI  - Spontaneous electrical activity of cardiomyocytes derived from hiPSCs of a patient with idiopathic ventricular fibrillation and RYR2 variant: impact of isoprenaline and varying concentrations of Ca2+
KW  - RYR2
KW  - idiopathic ventricular fibrillation
KW  - inhereted arrhythmia
KW  - hiPSC
KW  - MEA
UR  - https://escardio.sharepoint.com/sites/ESCEvents/Shared%20Documents/Forms/AllItems.aspx?id=%2Fsites%2FESCEvents%2FShared%20Documents%2FPublic%20shared%20documents%2FWorking%20group%20Events%2F2023%2FEWGCCE%20Meeting%202023%2FEWGCCE%5F2023%5Fabstract%5Fboo
N2  - Background: We have found a potentially proarrhythmic variant p. Y4734C in the ryanodine receptor type 2 (RYR2) in a patient suffering from idiopathic ventricular fibrillation. Here we bring pilot data showing the effect of 0.1 µM isoprenaline (ISO) and 0.5-5 mM Ca2+ on the spontaneous electrical activity of patient-specific cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM). Material and Methods: The spontaneous electrical activity of Y4734C-RYR2 hiPSC-CM (Y4734C) and hiPSC-CM of unrelated healthy control (WT) was recorded using the multielectrode array (MEA) technique at 37 °C. The cycle length (CL) and field potential duration (FPD and FPDc – correction according to Fridericia) are presented as the median ± interquartile range (IQR); non-parametric tests were used for comparison. Results: In control conditions (1.8 mM Ca2+), CL was insignificantly longer in WT (5.36±5.87 s; n=9) than in Y4734C (1.22±0.82 s; n=6). FDP and FPDc were significantly longer in WT (0.35±0.51 and 0.16±0.13 s, respectively; n=9) than in Y4734C (0.08±0.04 and 0.09±0.05 s, respectively; n=6; P˂0.05). Under the effect of 0.1 µM ISO, CL was shortened by 45.0±16.7% (n=9, P˂0.05) in WT and a similar, but insignificant change was observed in Y4734C (by 24.9±29.6%, n=5). We detected a significant CL prolongation in the presence of 1, 2, 3, and 5 mM Ca2+ in WT (P˂0.05) whereas it was not significantly changed in Y4734C. No significant changes in FPD and FPDc were observed both in ISO and varying concentrations of Ca2+ except for a shortened FPD in 0.1 µM ISO in WT. Conclusions: The pilot data showed longer FPD and FPDc in WT vs. Y4734C and significant changes mostly in CL in WT at 0.1 µM ISO and various Ca2+ concentrations.
ER  -

KRÁL, Martin, Olga ŠVECOVÁ, Štefan ZELENÁK, Jiří PACHERNÍK, Tomáš BÁRTA, Samuel LIETAVA, Iva SYNKOVÁ, Jana ZÍDKOVÁ, Tomáš NOVOTNÝ a Markéta BÉBAROVÁ. Spontaneous electrical activity of cardiomyocytes derived from hiPSCs of a patient with idiopathic ventricular fibrillation and RYR2 variant: impact of isoprenaline and varying concentrations of Ca2+. In \textit{47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2023}. 2023.

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