Publication details
Effect of isoprenaline and arrhythmogenic conditions on the spontaneous electrical activity of hiPSC-CM with Y4734C-RYR2 variant
| Authors | |
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| Year of publication | 2024 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Background: In a proband with idiopathic ventricular fibrillation (IF) and in his sister suffering from catecholaminergic polymorphic ventricular tachycardia (CPVT), p.Y4734C-RYR2 variant was found. Here we bring data showing the spontaneous electrical activity of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) of the proband (IF), his sister (CPVT), and his healthy nephew as control (WT), and its changes under arrhythmogenic conditions. Methods: The recordings by the multielectrode array technique were performed in control, i.e. in Tyrode solution with 5 mM K+ (5K++37°C), in 0.5 µM isoprenaline (ISO), and under cumulatively added hypokalemia (3K+), ß-adrenergic stimulation (ISO), and hyperthermia (40°C). Considering non-normal data distribution, the cycle length (CL) and its short-term variability (STVCL) are shown as the median from n samples and non-parametric tests were used. Results: In 5K+, CPVT hiPSC-CM had a significantly longer CL (1.47 s, n=19; P?0.05) than IF (1.05 s, n=32) and WT (0.77 s, n=7). ISO significantly shortened CL in all groups (by 38.3, 22.7, and 17.7 % in CPVT, IF, and WT, respectively, n=19, 32, and 7; P ? 0.05) and CPVT showed a significantly larger reaction than IF (P?0.05). The arrhythmogenic factors caused a significant increment in STVCL in IF (41.91 in 3K+, 22.65 in 3K++ISO, and 65.38 ms in 3K++ISO+40°C, vs. 10.23 ms in control; n=24; P?0.05) whereas it was significantly increased only in 3K+ in CPVT (21.14, 15.99, and 10.44 ms, respectively, vs. 13.13 in control; n=20; P?0.05). IF and CPVT significantly differed in STVCL in 3K++ISO+40°C. Conclusions: CPVT hiPSC-CM showed a lower frequency of spontaneous activity and its higher reactivity to ISO. An increment in beat-to-beat variability of CL was observed during arrhythmogenic conditions in IF hiPSC-CM. |
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