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.

Basic information

Original name

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+

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), Samuel LIETAVA (703 Slovakia), Iva SYNKOVÁ (203 Czech Republic), Jana ZÍDKOVÁ (203 Czech Republic), Tomáš NOVOTNÝ (203 Czech Republic) and Markéta BÉBAROVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Denmark

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Abstract book

RIV identification code

RIV/00216224:14110/23:00132099

Organization unit

Faculty of Medicine

Keywords (in Czech)

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

Keywords in English

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

Abstract

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.

Links

MUNI/A/1343/2022, interní kód MU

Name: Zátěže kardiovaskulárního systému od A po Z

Investor: Masaryk University, Loads on the cardiovascular system from A to Z

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, Samuel LIETAVA, Iva SYNKOVÁ, Jana ZÍDKOVÁ, Tomáš NOVOTNÝ and 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 and 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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