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In cardiovascular research, there is a high need to use reliable tools for modelling cardiovascular diseases (LQT, LEOPARD, Andersen-Tawil syndrome) and for cardiovascular drug testing. It is necessary that those models reflect human heart physiology. The most commonly used models are human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and transgenic animals, which showed promising results to study heart physiology. However, the existing hiPSC-CM and the animal models showed differences in electrophysiological properties due to immaturity and species differences. Therefore, it was of interest to study in detail the electrophysiological properties of the introduced models, hiPSC-CM and a Long QT-syndrome type 5 (LQT5) transgenic (LQT5-TG) rabbit model. The major results described in this thesis can be summarized as follows:  1. When studying the electrophysiological profile of hiPSC-CM, one of the major concerns is the low inward rectifier potassium current (IK1) and resting membrane potential (RMP). In our study, hiPSC-CM were cultivated in two different conditions. One was the conventional monolayer (ML), while the other was Engineered Heart Tissues (EHT). In our hiPSC-CM cell line we were able to measure IK1 comparable to human adult cardiomyocytes (CM). 2. In contrast to previous publications, we were able to measure resting membrane potential (RMP) values in a physiological range using sharp microelectrode in intact EHT. We showed that the low RMP measured by patch electrodes may be prone to error. 3. Patch-clamp experiments on ventricular myocytes isolated from LQT5-TG rabbits were performed. The results showed differences in IKs and IKr deactivation kinetics. The deactivation kinetics of the currents were accelerated. 4. At baseline, LQT5-TG animals showed slightly, but signicantly prolonged heart-rate corrected QT index (QTi) and increased STVQT. Dofetilide provoked Torsades de Pointes (TdP) arrhythmia in a larger number of LQT5-TG rabbits, paralleled by a further increase in short-term QT-interval variability (STVQT).

Investigation of antiarrhythmic and proarrhythmic mechanisms in modified systems with molecular biological methods