Detailed Information on Publication Record
2022
Translational research in the field of inherited arrhythmias
BÉBAROVÁ, Markéta, Olga ŠVECOVÁ, Larisa CHMELÍKOVÁ, Štefan ZELENÁK, Katarzyna Anna RADASZKIEWICZ et. al.Basic information
Original name
Translational research in the field of inherited arrhythmias
Authors
BÉBAROVÁ, Markéta (203 Czech Republic, guarantor, belonging to the institution), Olga ŠVECOVÁ (203 Czech Republic, belonging to the institution), Larisa CHMELÍKOVÁ (643 Russian Federation), Štefan ZELENÁK (703 Slovakia), Katarzyna Anna RADASZKIEWICZ (616 Poland), Jan HOŠEK (203 Czech Republic), Michal PÁSEK (203 Czech Republic, belonging to the institution), Tomáš BÁRTA (203 Czech Republic, belonging to the institution), Iva SYNKOVÁ (203 Czech Republic, belonging to the institution) and Tomáš NOVOTNÝ (203 Czech Republic, belonging to the institution)
Edition
Czech Cardiovascular Research and Innovation Days 2022, 2022
Other information
Language
English
Type of outcome
Konferenční abstrakt
Field of Study
30201 Cardiac and Cardiovascular systems
Country of publisher
Czech Republic
Confidentiality degree
není předmětem státního či obchodního tajemství
RIV identification code
RIV/00216224:14110/22:00129705
Organization unit
Faculty of Medicine
Keywords in English
inherited arrhythmias; translational research
Tags
Tags
International impact
Změněno: 4/5/2023 09:23, Mgr. Tereza Miškechová
Abstract
V originále
Inherited arrhythmias represent relatively rare, but life-threatening cardiac pathologies that are often associated with variants in cardiac ionic channel genes. A translational approach is essential to reveal the underlying arrhythmogenic mechanism and to find an improved treatment in the future. Since 2016, we have performed functional analysis in selected arrhythmia-associated heterozygous genetic variants, including the patch clamp and microelectrode array techniques and confocal microscopy, either on human ionic channels transfected in a cell line or on hiPSC-derived cardiomyocytes. Detailed analysis was performed in two KCNQ1 variants associated with LQTS. T309I resulted in a complete loss of function in the homozygous setting (impaired channel trafficking) and a dominant-negative effect in the heterozygous setting. In contrast, R562S showed preserved channel trafficking and, in the heterozygous setting, haploinsufficiency. The physiologically important beta-adrenergic stimulation was missing in R562S channels. In silico simulations suggested delayed afterdepolarizations as a likely arrhythmogenic mechanism in both variants. Cardiac ionic channel gene variants can be also detected in some patients suffering from the “true” idiopathic VF. We have recently started functional analysis in two probands, the first one carrying two KCNH2 variants (A228V and S1021Qfs*98) and the second one a single RYR2 variant (Y4734C). In Y4734C-RYR2 variant, the pilot data detected an irregular electric activity of the patient-specific cardiomyocytes at specific conditions; a detailed analysis will follow. Functional analysis is needed to reveal relationship between the identified genotype and phenotype. Identification of provoking circumstances that can result in unmasking of the phenotype in the “true” idiopathic VF could provide clinically-important data.
Links
| MUNI/A/1133/2021, interní kód MU |
| ||
| NU22-02-00348, research and development project |
| ||
| NV16-30571A, research and development project |
|