Spontaneous electrical activity of patient-specific
cardiomyocytes with a variant in the RYR2 gene recorded by
multielectrode array technique

a 2024

Spontaneous electrical activity of patient-specific cardiomyocytes with a variant in the RYR2 gene recorded by multielectrode array technique

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

Basic information

Original name

Spontaneous electrical activity of patient-specific cardiomyocytes with a variant in the RYR2 gene recorded by multielectrode array technique

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

IUPS Beacon Meeting 2024, 2024

Other information

Language

English

Type of outcome

Conference abstract

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Germany

Confidentiality degree

is not subject to a state or trade secret

RIV identification code

RIV/00216224:14110/24:00137555

Organization unit

Faculty of Medicine

Keywords in English

patient-specific cardiomyocytes; Y4734C; RYR2; multielectrode array; cycle length; short-term variability; field potential duration

Abstract

In the original language

Background: Y4734C variant in the ryanodine receptor type 2 (RYR2) was found in a patient with idiopathic ventricular fibrillation and his sister who was diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT). The variant hasn´t been functionally tested before. To reveal the proarrhythmic potential of the variant, cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) of the proband (IF), his sister (CPVT), and his healthy nephew as control (WT) were prepared. Here we bring data showing the spontaneous electrical activity of the hiPSC-CM and its changes under β-adrenergic stimulation. Methods: The spontaneous electrical activity of hiPSC-CM in control conditions (CC) and under the effect of 0.5µM isoprenaline (ISO) stimulating β-adrenergic receptors was recorded by the multielectrode array technique at 37C. The cycle length (CL) and field potential duration (FPD) were evaluated; Bazett´s formula was used to correct FPD (FPDc). The short-term variability of CL (STVCL) was calculated using Origin2024 software. The data are presented as the median±interquartile range of n samples (nWT=11; nIF=19; nCPVT=18), and non-parametric tests (Wilcoxon and Kruskal-Wallis) were used due to non-normal data distribution; P˂0.05 was considered statistically significant. Results: CL was significantly shorter in WT (0.71±0.29s) than in CPVT (1.40±0.81s); IF did not differ from both (1.10±1.23s). There was no difference between WT, IF, and CPVT in FPD (152.1±106.3, 148.5±75.9, and 128.0±46.0ms, respectively), however, FPDc was significantly longer in WT (179.1±139.1ms) than in CPVT (94.4±41.7ms). After adding ISO, CL and FPD were significantly shortened in all groups (WT CLISO=0.62±0.20s, FPDISO=135.2±58.3ms; IF CLISO=0.67±0.84s, FPDISO=118.7±71.8ms; CPVT CLISO=1.12±0.80s, FPDISO=104.4±25.7ms); no significant changes were observed in FPDc. The CPVT showed significantly larger shortening in CL than WT and IF (by 38.7±21.6, 13.8±23.3, and 25.7±28.5%, respectively) whereas no differences were apparent in FPD shortening. IF and CPVT showed significantly larger STVCL than WT in CC (18.3±45.1, 34.0±42.6, and 3.9±13.2ms, respectively). ISO significantly decreased STVCL in both IF and CPVT (9.0±27.8 and 8.5±7.8ms, respectively) but had no significant effect on WT (8.1±42.7ms). Conclusions: CPVT showed a slower beating rate than WT and higher reactivity to ISO than WT and IF. ISO increased beating frequency and shortened FPD in every group. IF and CPVT had higher beat-to-beat variability of CL than WT in CC, but no difference among groups was apparent under ISO.

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

Cite

KRÁL, Martin; Olga ŠVECOVÁ; Štefan ZELENÁK; Jiří PACHERNÍK; Tomáš BÁRTA; Jana ZÍDKOVÁ; Iva SYNKOVÁ; Samuel LIETAVA; Tomáš NOVOTNÝ and Markéta BÉBAROVÁ. Spontaneous electrical activity of patient-specific cardiomyocytes with a variant in the RYR2 gene recorded by multielectrode array technique. In IUPS Beacon Meeting 2024. 2024.

@proceedings{2449788,
   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 = {IUPS Beacon Meeting 2024},
   keywords = {patient-specific cardiomyocytes; Y4734C; RYR2; multielectrode array; cycle length; short-term variability; field potential duration},
   language = {eng},
   title = {Spontaneous electrical activity of patient-specific cardiomyocytes with a variant in the RYR2 gene recorded by multielectrode array technique},
   year = {2024}
}

TY  - CONF
ID  - 2449788
AU  - Král, Martin - Švecová, Olga - Zelenák, Štefan - Pacherník, Jiří - Bárta, Tomáš - Zídková, Jana - Synková, Iva - Lietava, Samuel - Novotný, Tomáš - Bébarová, Markéta
PY  - 2024
TI  - Spontaneous electrical activity of patient-specific cardiomyocytes with a variant in the RYR2 gene recorded by multielectrode array technique
KW  - patient-specific cardiomyocytes
KW  - Y4734C
KW  - RYR2
KW  - multielectrode array
KW  - cycle length
KW  - short-term variability
KW  - field potential duration
N2  - Background: Y4734C variant in the ryanodine receptor type 2 (RYR2) was found in a patient with idiopathic ventricular fibrillation and his sister who was diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT). The variant hasn´t been functionally tested before. To reveal the proarrhythmic potential of the variant, cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) of the proband (IF), his sister (CPVT), and his healthy nephew as control (WT) were prepared. Here we bring data showing the spontaneous electrical activity of the hiPSC-CM and its changes under β-adrenergic stimulation. Methods: The spontaneous electrical activity of hiPSC-CM in control conditions (CC) and under the effect of 0.5µM isoprenaline (ISO) stimulating β-adrenergic receptors was recorded by the multielectrode array technique at 37C. The cycle length (CL) and field potential duration (FPD) were evaluated; Bazett´s formula was used to correct FPD (FPDc). The short-term variability of CL (STVCL) was calculated using Origin2024 software. The data are presented as the median±interquartile range of n samples (nWT=11; nIF=19; nCPVT=18), and non-parametric tests (Wilcoxon and Kruskal-Wallis) were used due to non-normal data distribution; P˂0.05 was considered statistically significant. Results: CL was significantly shorter in WT (0.71±0.29s) than in CPVT (1.40±0.81s); IF did not differ from both (1.10±1.23s). There was no difference between WT, IF, and CPVT in FPD (152.1±106.3, 148.5±75.9, and 128.0±46.0ms, respectively), however, FPDc was significantly longer in WT (179.1±139.1ms) than in CPVT (94.4±41.7ms). After adding ISO, CL and FPD were significantly shortened in all groups (WT CLISO=0.62±0.20s, FPDISO=135.2±58.3ms; IF CLISO=0.67±0.84s, FPDISO=118.7±71.8ms; CPVT CLISO=1.12±0.80s, FPDISO=104.4±25.7ms); no significant changes were observed in FPDc. The CPVT showed significantly larger shortening in CL than WT and IF (by 38.7±21.6, 13.8±23.3, and 25.7±28.5%, respectively) whereas no differences were apparent in FPD shortening. IF and CPVT showed significantly larger STVCL than WT in CC (18.3±45.1, 34.0±42.6, and 3.9±13.2ms, respectively). ISO significantly decreased STVCL in both IF and CPVT (9.0±27.8 and 8.5±7.8ms, respectively) but had no significant effect on WT (8.1±42.7ms). Conclusions: CPVT showed a slower beating rate than WT and higher reactivity to ISO than WT and IF. ISO increased beating frequency and shortened FPD in every group. IF and CPVT had higher beat-to-beat variability of CL than WT in CC, but no difference among groups was apparent under ISO.
ER  -

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