Spontaneous electrical activity of patient-specific cardiomyocytes with a variant in the RYR2 gene recorded by multielectrode array technique
| Autoři | |
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| Rok publikování | 2024 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | 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 ß-adrenergic stimulation. Methods: The spontaneous electrical activity of hiPSC-CM in control conditions (CC) and under the effect of 0.5µM isoprenaline (ISO) stimulating ß-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. |
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