Empagliflozin, an inhibitor of sodium-glucose co-transporter 2 (iSGLT2), improves cardiovascular outcomes in patients with and without diabetes and possesses an antiarrhythmic activity. However, the mechanisms of these protective effects have not been fully elucidated. This study aimed to explore the impact of empagliflozin on ion channel activity and electrophysiological characteristics in the ventricular myocardium. The main cardiac ionic currents (I_Na, I_CaL, I_CaT, I_Kr, I_Ks) and action potentials (APs) were studied in zebrafish. Whole-cell currents were measured using the patch clamp method in the isolated ventricular cardiomyocytes. The conventional sharp glass microelectrode technique was applied for the recording of APs from the ventricular myocardium of the excised heart. Empagliflozin pretreatment compared to the control group enhanced potassium I_Kr step current density in the range of testing potentials from 0 to +30 mV, I_Kr tail current density in the range of testing potentials from +10 to +70 mV, and I_Ks current density in the range of testing potentials from −10 to +20 mV. Moreover, in the ventricular myocardium, empagliflozin pretreatment shortened AP duration APD as shown by reduced APD50 and APD90. Empagliflozin had no influence on sodium (I_Na) and L- and T-type calcium currents (I_CaL and I_CaT) in zebrafish ventricular cardiomyocytes. Thus, we conclude that empagliflozin increases the rapid and slow components of delayed rectifier K⁺ current (I_Kr and I_Ks). This mechanism could be favorable for cardiac protection.

Introduction. The development of heart failure is closely associated with the appearance of life threatening arrhythmias, which are often a terminal event for these patients. An analysis of randomized clinical trials of inhibitors of sodium-glucose cotransporter type 2 indicates the clinically significant potential of these drugs as agents with antiarrhythmic properties. However, at the moment the full mechanism by which this effect can be realized is still not fully understood.Aim. To evaluate the effect of empagliflozin on the transmembrane calcium currents and the intracellular calcium transients on isolated ventricular cardiomyocytes of mice under conditions of normoglycemia.Materials and methods. In the experiment, ventricular cardiomyocytes were isolated from 12 outbred male mice. 2 groups were formed: group № 1 – control ventricular cardiomyocytes; group № 2 – ventricular cardiomyocytes after two hours incubation with 5 µmol/L empagliflozin solution. Transmembrane calcium currents were recorded and intracellular calcium transients were assessed.Results and discussion. Incubation of ventricular cardiomyocytes with empagliflozin significantly increased I_Ca current density and accelerated Ca²⁺ temporal dynamics. The amplitude of the Ca²⁺ wave and the rate of rise and decay were increased and the duration of the Ca²⁺ wave was shortened.Conclusion. The result of the experiment indicates that empagliflozin is able to modulate Ca²⁺-dependent mechanism of the excitation-contraction-coupling, enhancing and accelerating Ca²⁺ release into cytoplasm and reuptake. This presumably can optimize, namely reduce the time of systole and enhance it, which may be one of the important elements in the manifestation of empagliflozin antiarrhythmic properties.

The latest scientific data of the development, structure and cellular composition of thymus are studied and presented. Both widely known sources and new literature were used. This article is reporting external features of the structure of the thymus, internal structure, cellular composition. In particular, attention is paid to the description of the thymus zones, because there has been no consensus among morphologists in this matter. Embryonic development is described, as well as morphometric parameters in different periods of prenatal development. This article will be useful in writing scientific and certificating work, books and dissertation dealing the development of thymus, because there is more actually information about this theme.

Variants in MYPN encoding a sarcomeric protein, myopalladin, are associated with different types of cardiomyopathies and myopathies. However, molecular mechanisms of MYPN-associated pathologies are still poorly understood. In this study, we generated induced pluripotent stem cells (iPSCs) from a hypertrophic cardiomyopathy patient carried a novel p.N989I (c.2966A>T) variant in MYPN and used iPSC-derived cardiomyocytes to examine the impact of the variant on biophysical characteristics and transcriptomic profile. No significant changes in parameters of calcium transient, sodium current and action potential were found in iPSC-derived cardiomyocytes with p.N989I (c.2966A>T) variant in MYPN compared to control cells from a healthy donor. At the transcriptomic level, MYPN-N989I cardiomyocytes demonstrated an upregulation of genes linked to cell cycle, division springle, microtubule cytoskeleton organization and myogenic program genes. A downregulation of sarcomeric, Z-disc- and cell junction-associated genes and genes involved in ATP synthesis, oxidative phosphorylation and SRF-signaling pathway was also revealed. Our data suggest that the p.N989I (c.2966A>T) variant in MYPN plays a dual role in hypertrophic cardiomyopathy pathogenesis, disrupting not only sarcomeric and cytoskeletal organization but also muscle gene program regulation.