a 2022

Action potential characteristics in derived cardiomyocytes of a patient carrying RYR2 variant

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

Základní údaje

Originální název

Action potential characteristics in derived cardiomyocytes of a patient carrying 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), Iva SYNKOVÁ (203 Česká republika, domácí), Tomáš NOVOTNÝ (203 Česká republika, domácí) a Markéta BÉBAROVÁ (203 Česká republika, garant, domácí)

Vydání

49. pracovní konference Komise experimentální kardiologie, 2022

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Slovensko

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14110/22:00129702

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

derived cardiomyocytes; RYR2 variant

Štítky

Příznaky

Mezinárodní význam
Změněno: 26. 4. 2023 09:31, Mgr. Tereza Miškechová

Anotace

V originále

Ventricular fibrillation (VF) is a common cause of death in young adults. It can originate from a dysfunction of a cardiac ionic channel which may be caused by a variant in the encoding gene. We have found a potentially proarrhythmic variant in the RyR2 gene, p.Y4734C-RYR2, in a patient with VF, but structurally and functionally healthy heart (no signs of heart impairment on magnetic resonance, echocardiography, and electrocardiography both at rest and after exercise; i.e. idiopathic VF). This variant has not been functionally tested yet. RYR2 channel variants are usually associated with an inherited arrhythmogenic syndrome called catecholaminergic polymorphic ventricular tachycardia (CPVT). It might also apply to this variant because a sister of the proband suffers from this disease as has been recently revealed. However, no signs of CPVT could be identified in the proband. Hence, the dysfunction might be masked by other electrophysiological changes in his heart. To reveal the mechanism and specific conditions that may lead to VF in the proband, we have recently started a functional analysis of the Y4734C-RYR2 variant using cardiomyocytes derived from patient-specific human-induced pluripotent stem cells (hiPSC). It is a clinically relevant, up-to-date model that enables fast transmission of the experimentally acquired data to clinical practice. Here we bring pilot data showing basic characteristics of spontaneous action potential waveforms in Y4734C-RYR2 cardiomyocytes in comparison with the characteristics in hiPSC-derived cardiomyocytes of an unrelated healthy control (WT-RYR2; methods: whole-cell patch-clamp technique, at 37C, 5 and 6 samples in Y4734C-RYR2 and WT-RYR2 cardiomyocytes, respectively). No significant differences have been identified. We just observed a tendency to an increased beating rate and decreased action potential duration in Y4734C-RYR2 cardiomyocytes; the latter remained even after correction of the action potential duration to the respective beating rate using both Bazett´s and Fridericia´s formulas. For a better understanding of the influence of this variant, we will have to perform more measurements and analyse changes in action potential configuration at specific conditions. It will help us to better understand the mechanism of VF generation in the proband which might be essential for his treatment and prevention of life-threatening VF episodes in the future.

Návaznosti

MUNI/A/1133/2021, interní kód MU
Název: Od buňky k medicíně (Akronym: CELLVIEW)
Investor: Masarykova univerzita, Od buňky k medicíně
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