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.

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.

Discrete Stretch Eliminates Electrophysiological Dose-Dependent Effects of Nitric Oxide Donor SNAP in Rat Atrium.

Depolarization of cardiomyocytes triggered by stretch and activation of mechanically gated ion channels can lead to serious arrhythmias. However, stretch-induced signaling activating these channels remain little studied. This study tested the hypothesis on implication of NO in shaping the electrical abnormalities provoked by stretch of the right atrial myocardium in rat via a mechanism engaging a signaling cascade, where NO plays a significant role.

Interleukin-6 induced activation of a non-selective outward cation conductance in human cardiac fibroblasts.

Background: It has been demonstrated that cardiac fibroblasts of the human heart have several myocyte-like features, induced by inflammation.

Objectives: This study analyzed the changes of the expressed currents in the basal condition and in the presence of interleukin-6 in cultured human cardiac fibroblasts.

Methods: Human cardiac fibroblasts were cultured as monolayers from earlier passages (2-4).

Cytokine Effects on Mechano-Induced Electrical Activity in Atrial Myocardium.

Unlabelled: The role of cytokines as regulators of stretch-related mechanisms is of special importance since mechano-sensitivity plays an important role in a wide variety of biological processes. Here, we elucidate the influence of cytokine application on mechano-sensitivity and mechano-transduction. The atrial myocardial stretch induces production of interleukin (IL)-2, IL-6, IL-13, IL-17A, and IL-18 with exception of tumor necrosis factor α (TNF-α), IL-1β, and vascular endothelial growth factor B (VEGF-B).

Role of nitric oxide in the regulation of mechanosensitive ionic channels in cardiomyocytes: contribution of NO-synthases.

The role of NO in the regulation of currents passing through ion channels activated by cell stretching (mechanically gated channels, MGC), particularly through cation-selective K(+)-channels TRPC6, TREK1 (K(2P)2.1), and TREK2 (K(2P)10.1), was studied on isolated mouse, rat, and guinea pig cardiomyocytes using whole-cell patch-clamp technique.

Role of nitric oxide in activity control of mechanically gated ionic channels in cardiomyocytes: NO-donor study.

Whole-cell ionic currents through mechanically gated channels (MGC) were recorded in isolated cardiomyocytes under voltage clamp conditions. In unstrained cells, NO donors SNAP and DEA-NO activated MGC and induced MG-like currents. In contrast, in stretched cells with activated MGC, these NO-donors inactivated and inhibited MGC.

Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels.

Hyperforin, a bicyclic polyprenylated acylphloroglucinol derivative, is the main active principle of St. John's wort extract responsible for its antidepressive profile. Hyperforin inhibits the neuronal serotonin and norepinephrine uptake comparable to synthetic antidepressants.

Receptor-induced activation of Drosophila TRP gamma by polyunsaturated fatty acids.

Cellular calcium homeostasis is regulated by hormones and neurotransmitters, resulting in the activation of a variety of proteins, in particular, channel proteins of the plasma membrane and of intracellular compartments. Such channels are, for example, TRP channels of the TRPC protein family that are activated by various mediators from receptor-stimulated signaling cascades. In Drosophila, two TRPC channels, TRP and TRPL, are involved in phototransduction.

Na(+)-Ca(2+) exchanger overexpression predisposes to reactive oxygen species-induced injury.

Objective: In heart failure (HF), the generation of reactive oxygen species (ROS) is enhanced. It was shown that failing cardiac myocytes are more susceptible to ROS-induced damage, possibly due to increased expression of the sarcolemmal Na-Ca exchanger (NCX).

Methods: We investigated the consequences of increased expression levels of NCX in adult rabbit ventricular cardiomyocytes (via adenovirus-mediated gene transfer, Ad-NCX1-GFP) with respect to tolerance towards ROS.

Differential effects of stretch and compression on membrane currents and [Na+]c in ventricular myocytes.

Mechano-electrical feedback was studied in the single ventricular myocytes. A small fraction (approximately 10%) of the cell surface could be stretched or compressed by a glass stylus. Stretch depolarised, shortened the action potential and induced extra systoles.

Mechanically induced potentials in rat atrial fibroblasts depend on actin and tubulin polymerisation.

When atrial tissue contracts, mechanically induced potentials (MIPs) are generated in fibroblasts, presumably by activation of a non-selective cation conductance Gns. Non-stimulated atrial fibroblasts had a mean (+/-SD) membrane potential (Em) of -22 +/- 2 mV and an input resistance of 510 +/- 10 MS. MIP amplitude (AMIP) was 38+/-4 mV when current injection had polarised Em to Vm = -50 mV.