Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation
| Authors | |
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| Year of publication | 2023 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Background: The RYR2 variant Y4734C was identified in a patient suffering from idiopathic ventricular fibrillation. To investigate its pathogenic character, functional analysis has been started. Here, we present the pilot data on potential proarrhythmic stimuli in this variant. Material and Methods: The recordings of the spontaneous electrical activity of Y4734C-RYR2 (Y4734C) and unrelated healthy control (WT) hiPSC-CM (5 and 3 measured samples, respectively) were performed using the multielectrode array (MEA) technique at 37°C. Besides the evaluation of the cycle length (CL), the short-term variability of CL (STVCL) was calculated. Since some data were not normally distributed, the median ± interquartile range (IQR) and non-parametric statistical tests were used. Results: In the control Tyrode solution (5 mM K+ Tyr), CL significantly differed in WT and Y4734C (1.36±0.22 and 0.53±0.14 s, respectively; P ? 0.05), but STVCL was the same (8.0 ms). Subsequently, the possible proarrhythmic impact of additively applied hypokalaemia (3 mM K+), ß-adrenergic stimulation (1 µM isoprenaline), and high temperature (40°C) was tested. In Y4734C, STVCL slightly decreased in 3 mM K+ and then gradually increased when 1 µM isoprenaline was added, first alone and later in combination with 40°C (4.1, 22.4, and 39.3 ms, respectively; P ? 0.05). In contrast, STVCL in WT was considerably higher only in the concurrent presence of 3 mM K+ and 1 µM isoprenaline (30.7 ms vs. 13.3 ms in 3 mM K+ and 9.3 ms in the presence of all the stimuli; P ? 0.05). Conclusions: The pilot data showed non-significant differences between the effect of three selected proarrhythmic stimuli, namely hypokalaemia, ß-adrenergic stimulation, and high temperature, on the spontaneous electrical activity of WT- and Y4734C-RYR2 hiPSC-CM. |
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