The Role of K Channels in Atrial Fibrillation.

This manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (K) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of K channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of K activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.

Simulated Microgravity and Hypergravity Affect the Expression Level of Soluble Guanylate Cyclase, Adenylate Cyclase, and Phosphodiesterase Genesin Rat Ventricular Cardiomyocytes.

Ion channels activity is regulated through soluble guanylate cyclase (sGC) and adenylate cyclase (AC) pathways, while phosphodiesterases (PDE) control the intracellular levels of cAMP and cGMP. Here we applied RNA transcriptome sequencing to study changes in the gene expression of the sGC, AC, and PDE isoforms in isolated rat ventricular cardiomyocytes under conditions of microgravity and hypergravity. Our results demonstrate that microgravity reduces the expression of sGC isoform genes, while hypergravity increases their expression.

Transcriptomic profile of the mechanosensitive ion channelome in human cardiac fibroblasts.

Human cardiac fibroblasts (HCFs) have mRNA transcripts that encode different mechanosensitive ion channels and channel regulatory proteins whose functions are not known yet. The primary goal of this work was to define the mechanosensitive ion channelome of HCFs. The most common type of cationic channel is the transient receptor potential (TRP) family, which is followed by the TWIK-related K channel (TREK), transmembrane protein 63 (TMEM63), and PIEZO channel (PIEZO) families.

Simulated Microgravity Changes the Number of Mechanically Gated and Mechanosensitive Ion Channels Genes Transcripts in Rat Ventricular Cardiomyocytes.

The mechanoelectrical feedback in the heart is based on the work of mechanically gated (MGCs) and mechanosensitive (MSCs) channels. Since microgravity alters the heart's morphological and physiological properties, we hypothesized that the expression of both MGCs and MSCs would be affected. We employed RNA transcriptome sequencing to investigate changes in the gene transcript levels of MGCs and MSCs in isolated rat ventricular cardiomyocytes under control conditions and in a simulated microgravity environment.

Hypergravity Increases the Number of Gene Transcripts of Mechanically Gated and Mechanosensitive Ion Channels in Rat Ventricular Cardiomyocytes.

Since hypergravity changes the morphological and physiological properties of the heart, it was assumed that the expression of ion channels that respond to cell stretching or compressing, mechanically gated channels (MGC) and mechanosensitive channels (MSC), would be affected. Using RNA transcriptome sequencing, the change in the number of transcripts for MGC and MSC genes was studied in isolated rat ventricular cardiomyocytes under 4g hypergravity for 5 days. It was shown for the first time that hypergravity induces changes in the number of transcripts of MGC genes: an increase for TRPC1, TRPC3, TRPM7, TRPP1 (PKD1), TRPP2 (PKD2), TMEM63A, TMEM63B, but a decrease for TRPV2, Piezo1, Piezo2.

Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Cacurrent.

Background: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through Ca1.

The role of activation of two different sGC binding sites by NO-dependent and NO-independent mechanisms in the regulation of SACs in rat ventricular cardiomyocytes.

The mechanoelectrical feedback (MEF) mechanism in the heart that plays a significant role in the occurrence of arrhythmias, involves cation flux through cation nonselective stretch-activated channels (SACs). It is well known that nitric oxide (NO) can act as a regulator of MEF. Here we addressed the possibility of SAC's regulation along NO-dependent and NO-independent pathways, as well as the possibility of S-nitrosylation of SACs.

Gadolinium as an Inhibitor of Ionic Currents in Isolated Rat Ventricular Cardiomyocytes.

The whole-cell patch-clamp technique was used to examine the effect of gadolinium Gd (a non-specific blocker of mechanically gated current I, a component of late current I) on ionic currents in insolated rat ventricular cardiomyocytes alone and in combination with the blockers of L-type calcium currents (I) nifedipine (10 μM) or verapamil (1 μM). In K/K or Cs/Cs media, blockade of I produced no effect on I at negative potentials, but inhibited I at positive ones. In K/K medium, Gd (5 μM) decreased the net persistent current (I) at -45 mV from 198.

Participation of PKG and PKA-related pathways in the IFN-γ induced modulation of the BK channel activity in human cardiac fibroblasts.

This study was devoted to elucidating the interferon (IFN)-γ-induced signaling pathway and the interaction between protein kinase G (PKG) and protein kinase A (PKA) through large-conductance Ca(2+)-activated K(+) channels in human cardiac fibroblasts. The I currents were recorded using a whole-cell patch clamp method. A large depolarization (+50 mV) and a high Ca concentration (pCa 6.

Long-Term IL-2 Incubation-Induced L-type Calcium Channels Activation in Rat Ventricle Cardiomyocytes.

The following study examined the impact of IL-2 on Ca channel activity in the event of several hours' incubation in IL-2. The right ventricle free wall for action potential measurements was isolated and perfused with Tyrode solution. The whole-cell voltage clamp experiments were performed on enzymatically isolated single cardiomyocytes.

Metabolic Restructuring in the Liver under Conditions of Endogenous Intoxication.

Significant metabolic alterations in the liver were observed in dogs with modeled acute peritonitis. These changes significantly impaired detoxification function of the liver, which was seen from the increase in the titer of toxic products in the early post-surgery period not only in the lymph, but also in the blood plasma. The key pathogenic mechanism leading to acute liver failure is destabilization of cell membrane resulting from LPO, phospholipase activity, and tissue hypoxia.

Effect of Successive Administration of Vancomycin and Amikacin on Auditory Function of Immature Animals.

Effect of successive administration vancomycin and amikacin in therapeutic doses on immature auditory organ was compared to single administration of the same drugs in chronic experiments on immature rabbits by recording of short-latency auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Drug administration always increased significantly the ABR peak I threshold. Ototoxic antibiotics did not change DPOAE, but selectively affected activity of outer hair cells.

Antiproliferative Effects of Modified Bioflavonoid in Ex Vivo Model.

We studied the effect of modified bioflavonoid and reference drug quercetin dihydrate on proliferation of mononuclears triggered by T- and B-cell mitogens. Lymphocytes were in vivo pretreated with the examined agents followed by their explantation and in vitro activation with T- and B-cell mitogens in cell culture. Intraperitoneal injection of modified bioflavonoid and quercetin dihydrate produced a dose-dependent inhibition of proliferation of the in vitroactivated splenocytes; modified bioflavonoid demonstrated higher antiproliferative activity.

[Hemoglobin oxygen transport capacity in surgical endotoxicosis ].

In surgical endointoxication hemoglobin oxygen transport capacity of red blood cells (hemoglobin affinity ligands: the ability to bind and release ligands) is reduced and is associated with the severity of endogenous intoxication. Violation of oxygen transport function of hemoglobin at endogenous intoxication is associated with conformational changes of a biomolecule, and its possible influence on reactive oxygen species, which confirmed in experiments in vitro: under the influence of oxygen-iron ascorbate ability of hemoglobin deteriorates. Largely similar structural and functional changes in hemoglobin occur in patients with surgical endotoxicosis.

Evaluation of the Effect of Modified Bioflavonoid and Quercetin Dihydrate on Cytokine Secretion by Mitogen-Activated Mononuclear Cells.

An experimental study revealed the effect on modified bioflavonoid on the inhibition of secretion of IFN-γ and IL-2 by ConA-stimulated mononuclear cells. These changes were accompanied by an increase in the secretion of IL-17 and IL-6. Our results suggest the differentiation of CD4(+) T helper cells into Th1 and Th17 subpopulations.

Auditory Function in Immature Animals after Two Consecutive Courses of Ototoxic Antibiotics.

In chronic experiments on immature rabbits receiving therapeutic courses of vancomycin, gentamicin, and consecutive administration of vancomicin and gentamicin by the scheme used in neonatology, hearing function was evaluated by the methods of auditory evoked potentials (auditory brainstem response, ABR) and distortion product otoacoustic emission (DPOAE). Comparison with the control group revealed ototoxic effects of all studied antibiotics that manifested in increased sound tolerance and more rapid shortening of latencies in 30-100 dB range. Higher thresholds were found only after gentamicin administration.