Tropical teleost fish Danio rerio is increasingly used as a model object for electrophysiological studies of human cardiac physiology and pathology. D. rerio is characterized by the similarity with humans in such functional parameters of the electrical activity of the heart as heart rate, action potential morphology, as well as in a set of ion currents depolarizing and repolarizing the cell membrane. D. rerio is easy to breed, easy to handle experimentally, and easy to genetically modify. This overview presents current data on the structural and functional organization of ion channels in D. rerio heart myocytes.

Phenanthrene (Phen) is one of the widespread species of polyaromatic hydrocarbons, a tricyclic compound, component of crude oil and diesel fuel. Earlier studies have shown its negative effects on fish heart function that may explain the toxicity of this pollutant. The present study aimed to elucidate the cardiac electrophysiological effects of Phen in shorthorn sculpin, the widespread and common fish of the Arctic region using the patch-clamp technique. We have found pronounced effects of Phen on the duration and upstroke velocity of action potentials (APs) in sculpin ventricular myocytes. 1 µM Phen produced almost two-fold prolongation of AP duration measured at 90 velocity of AP. These effects are attributed to suppression of K+ rapid delayed rectifier current IKr (IC50 = 144 nM) and fast Na+ current INa (IC50 = 5.85 µM). Resting membrane potential and K+ inward rectifier current IK1 were not affected by Phen even in the maximal concentration of 30 µM. Thus, low concentrations of Phen induce changes in cellular electrical activity of sculpin ventricular myocytes which might lead to proarrhythmic effects such as slowing of repolarization and decrease in excitation conduction velocity at the tissue level.

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 ICa 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.

BACKGROUND:Brugada syndrome (BrS) is a rare inherited cardiac arrhythmia with increased risk of sudden cardiac death. Mutations in gene SCN5A, which encodes the α-subunit of cardiac voltage-gated sodium channel NaV1.5, have been identified in over 20% of patients with BrS. However, only a small fraction of NaV1.5 variants, which are associated with BrS, are characterized in electrophysiological experiments.RESULTS:Here we explored variants V281A and L1582P, which were found in our patients with BrS, and variants F543L and K1419E, which are reportedly associated with BrS. Heterologous expression of the variants in CHO-K1 cells and the Western blot analysis demonstrated that each variant appeared at the cell surface. We further measured sodium current in the whole-cell voltage clamp configuration. Variant F543L produced robust sodium current with a hyperpolarizing shift in the voltage dependence of steady-state fast inactivation. Other variants did not produce detectable sodium currents, indicating a complete loss of function. In a recent cryoEM structure of the hNaV1.5 channel, residues V281, K1419, and L1582 are in close contacts with residues whose mutations are reportedly associated with BrS, indicating functional importance of respective contacts.CONCLUSIONS:Our results support the notion that loss of function of NaV1.5 or decrease of the channel activity is involved in the pathogenesis of BrS.

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 (INa, ICaL, ICaT, IKr, IKs) 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 IKr step current density in the range of testing potentials from 0 to +30 mV, IKr tail current density in the range of testing potentials from +10 to +70 mV, and IKs 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 (INa) and L- and T-type calcium currents (ICaL and ICaT) in zebrafish ventricular cardiomyocytes. Thus, we conclude that empagliflozin increases the rapid and slow components of delayed rectifier K+ current (IKr and IKs). This mechanism could be favorable for cardiac protection.

Genetic variants in the ABCC9 gene, encoding the SUR2 auxiliary subunit from KATP channels, were previously linked with various inherited diseases. This wide range of congenital disorders includes multisystem and cardiovascular pathologies. The gain-of-function mutations result in Cantu syndrome, acromegaloid facial appearance, hypertrichosis, and acromegaloid facial features. The loss-of-function mutations in the ABCC9 gene were associated with the Brugada syndrome, early repolarization syndrome, and dilated cardiomyopathy. Here, we reported a patient with a loss-of-function variant in the ABCC9 gene, identified by target high-throughput sequencing. The female proband presented with several episodes of ventricular fibrillation and hypokalemia upon emotional stress. This case sheds light on the consequences of KATP channel dysfunction in the cardiovascular system and underlines the complexity of the clinical presentation of ABCC9-related diseases.

The most important component of the filtration apparatus of the renal glomeruli is specialized visceral epithelial cells podocytes. The normal physiological function of podocytes is critically dependent on the proper regulation of the intracellular Ca2+ content; excessive Ca2+ influx in cells can lead to a disorder of cell morphology, podocytopathy, apoptosis and subsequent glomeruli damage. Podocytopathy is one of the primary characteristics of proteinuria and focal segmental glomerulosclerosis. One of the key proteins responsible for Ca2+ influx in podocytes is the TRPC6 channel. Since the first discovery of a mutation in a gene encoding TRPC6, the attention of the scientific community has been focused on studying the role of this ion channel in the onset and development of kidney diseases. Both an increase and a decrease in the functional activity of TRPC6 are associated with the manifestation of severe nephrotic syndromes leading to the end-stage of chronic kidney disease. The review contains materials related to the regulation of TRPC6 activity and the role of this channel in the pathogenesis of glomerular diseases.

Adipose tissue is an endocrine organ secreting signal peptides adipokines. Adipokines play a significant role in the regulation of the immune, endocrine, nervous, excretory systems. Adipokine imbalance leads to chronic inflammation, metabolic and cardiovascular diseases. Obesity as the primary reason of the adipokine imbalance is the leading risk factor of hypertension, atherosclerosis and coronary artery disease. Thus, experimental and clinical studies of adipokine biology are essential for the development of the novel therapeutic approaches for the management of cardiometabolic diseases. This review focuses on the role of adiponectin, leptin, chemerin, omentin and visfatin in physiological and pathophysiological processes in the cardiovascular system.