Spontaneous electrical activity of cardiomyocytes derived from hiPSCs of a patient with idiopathic ventricular fibrillation and RYR2 variant: impact of isoprenaline and varying concentrations of Ca2+
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| Year of publication | 2023 |
| Type | Conference abstract |
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| Citation | |
| Description | Background: We have found a potentially proarrhythmic variant p. Y4734C in the ryanodine receptor type 2 (RYR2) in a patient suffering from idiopathic ventricular fibrillation. Here we bring pilot data showing the effect of 0.1 µM isoprenaline (ISO) and 0.5-5 mM Ca2+ on the spontaneous electrical activity of patient-specific cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM). Material and Methods: The spontaneous electrical activity of Y4734C-RYR2 hiPSC-CM (Y4734C) and hiPSC-CM of unrelated healthy control (WT) was recorded using the multielectrode array (MEA) technique at 37 °C. The cycle length (CL) and field potential duration (FPD and FPDc – correction according to Fridericia) are presented as the median ± interquartile range (IQR); non-parametric tests were used for comparison. Results: In control conditions (1.8 mM Ca2+), CL was insignificantly longer in WT (5.36±5.87 s; n=9) than in Y4734C (1.22±0.82 s; n=6). FDP and FPDc were significantly longer in WT (0.35±0.51 and 0.16±0.13 s, respectively; n=9) than in Y4734C (0.08±0.04 and 0.09±0.05 s, respectively; n=6; P?0.05). Under the effect of 0.1 µM ISO, CL was shortened by 45.0±16.7% (n=9, P?0.05) in WT and a similar, but insignificant change was observed in Y4734C (by 24.9±29.6%, n=5). We detected a significant CL prolongation in the presence of 1, 2, 3, and 5 mM Ca2+ in WT (P?0.05) whereas it was not significantly changed in Y4734C. No significant changes in FPD and FPDc were observed both in ISO and varying concentrations of Ca2+ except for a shortened FPD in 0.1 µM ISO in WT. Conclusions: The pilot data showed longer FPD and FPDc in WT vs. Y4734C and significant changes mostly in CL in WT at 0.1 µM ISO and various Ca2+ concentrations. |
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