Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome.

We identified a single nucleotide variation (SNV) (c.1264A > G) in the KCNQ1 gene in a 5-year-old boy who presented with a prolonged QT interval. His elder brother and mother, but not sister and father, also had this mutation.

α1-adrenergic receptors accompanied by GATA4 expression are related to proarrhythmic conduction and automaticity in rat interatrial septum.

The development of interatrial septum (IAS) is a complicated process, which continues during postnatal life. The hypertrophic signals in developing heart are mediated among others by α-adrenergic pathways. These facts suggest the presence of specific electrophysiological features in developing IAS.

MicroRNA miR-133a-3p Facilitates Adrenergic Proarrhythmic Ectopy in Rat Pulmonary Vein Myocardium by Increasing cAMP Content.

Cardiac-specific microRNA miR-133a-3p modulates adrenergic signaling. Adrenergic receptors and their intracellular pathways are the key players in proarrhythmic ectopy derived from the myocardial sleeves of the pulmonary veins. We studied the effect of miR-133a-3p on ectopy induced by norepinephrine in myocardial tissue of rat pulmonary veins.

Ionic currents underlying different patterns of electrical activity in working cardiac myocytes of mammals and non-mammalian vertebrates.

The orderly contraction of the vertebrate heart is determined by generation and propagation of cardiac action potentials (APs). APs are generated by the integrated activity of time- and voltage-dependent ionic channels which carry inward Na and Ca currents, and outward K currents. This review compares atrial and ventricular APs and underlying ion currents between different taxa of vertebrates.

Adrenergic prolongation of action potential duration in rainbow trout myocardium via inhibition of the delayed rectifier potassium current, I.

Catecholamines mediate the 'fight or flight' response in a wide variety of vertebrates. The endogenous catecholamine adrenaline increases heart rate and contractile strength to raise cardiac output. The increase in contractile force is driven in large part by an increase in myocyte Ca influx on the L-type Ca current (I) during the cardiac action potential (AP).

Micro-RNA 133a-3p induces repolarization abnormalities in atrial myocardium and modulates ventricular electrophysiology affecting I and Ito currents.

Mir-133a-3p is the most abundant myocardial microRNA. The impact of mir-133a-3p on cardiac electrophysiology is poorly explored. In this study, we investigated the effects of mir-133a-3p on the main ionic currents critical for action potential (AP) generation and electrical activity of the heart.

Repolarizing potassium currents in working myocardium of Japanese quail: a novel translational model for cardiac electrophysiology.

Birds developed endothermy and four-chambered high-performance heart independently from mammals. Though avian embryos are extensively studied and widely used as various models for heart research, little is known about cardiac physiology of adult birds. Meanwhile, cardiac electrophysiology is in search for easily accessible and relevant model objects which resemble human myocardium in the pattern of repolarizing currents (I, I, I and I).

Attenuation of inward rectifier potassium current contributes to the α1-adrenergic receptor-induced proarrhythmicity in the caval vein myocardium.

Aim: This study is aimed at investigation of electrophysiological effects of α1-adrenoreceptor (α1-AR) stimulation in the rat superior vena cava (SVC) myocardium, which is one of the sources of proarrhythmic activity.

Methods: α1-ARs agonists (phenylephrine-PHE or norepinephrine in presence of atenolol-NE + ATL) were applied to SVC and atrial tissue preparations or isolated cardiomyocytes, which were examined using optical mapping, glass microelectrodes or whole-cell patch clamp. α1-ARs distribution was evaluated using immunofluorescence.

Small G-protein RhoA is a potential inhibitor of cardiac fast sodium current.

Small G-proteins of Rho family modulate the activity of several classes of ion channels, including K channels Kv1.2, Kir2.1, and ERG; Ca channels; and epithelial Na channels.

Regulation of Na1.5 Sodium Channels by Small G-Proteins of the Rho Family in a Heterologous Expression System.

The effect of small G-proteins of the Rho family on sodium current conducted by cardiac isoform Na1.5 of voltage-gated sodium channels was studied in heterologous expression system, CHO-K1 cell line transfected with a plasmid containing the Na1.5 gene.

Identification of Key Small Non-Coding MicroRNAs Controlling Pacemaker Mechanisms in the Human Sinus Node.

Background The sinus node (SN) is the primary pacemaker of the heart. SN myocytes possess distinctive action potential morphology with spontaneous diastolic depolarization because of a unique expression of ion channels and Ca-handling proteins. MicroRNAs (miRs) inhibit gene expression.

Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner.

Extracellular ATP and nicotinamide adenine dinucleotide (β-NAD) demonstrate properties of neurotransmitters and neuromodulators in peripheral and central nervous system. It has been shown previously that ATP and β-NAD affect cardiac functioning in adult mammals. Nevertheless, the modulation of cardiac activity by purine compounds in the early postnatal development is still not elucidated.

Extracellular NAD Suppresses Adrenergic Effects in the Atrial Myocardium of Rats during the Early Postnatal Ontogeny.

The effects of sympathetic cotransmitter NAD+ (10 μM) on bioelectric activity of the heart under conditions of adrenergic stimulation were studied on isolated spontaneously contracting preparations (without stimulation) of the right atrium from 2-7-day-old rats. Action potentials were recorded in the working myocardium using standard microelectrode technique. Perfusion of the right atrium with norepinephrine solution (1 μM) altered the configuration and significantly lengthened the action potentials.

Negative inotropic effects of diadenosine tetraphosphate are mediated by protein kinase C and phosphodiesterases stimulation in the rat heart.

Extracellular diadenosine polyphosphates (ApA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApA cause alteration of the heart functioning via purine receptors in different mammalian species. Nevertheless, principal intracellular pathways which underlie ApA action in the heart remain unknown.

Diadenosine Polyphosphates Suppress the Effects of Sympathetic Nerve Stimulation in Rabbit Heart Pacemaker.

The modulatory influence of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) on the effect of intramural autonomic nerve stimulation in isolated rabbit sinoatrial node were examined. Electrical activity of the sinoatrial node was recorded intracellularly. Against the background of blockade of adrenergic effects with propranolol (3×10 M) or in preparations isolated 2 h after injection of reserpine (2 mg/kg), nerve stimulation induced short-term membrane hyperpolarization and diminished the sinus node firing rate.

Kinetics of Mechanical Stretch-Induced Nitric Oxide Production in Rat Ventricular Cardiac Myocytes.

Discrete mechanical stretch of isolated spontaneously contracting cardiac myocytes was employed to examine the kinetics of NO production in these cells. NO oscillations were detected with fluorescent dye 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate. The mechanisms underlying stretch-induced changes in NO concentration remain unclear and further studies are needed to evaluate the role of NO oscillation in the regulation of cardiomyocyte function.

Effect of Purine Co-Transmitters on Automatic Activity Caused by Norepinephrine in Myocardial Sleeves of Pulmonary Veins.

We studied the effect of extracellular purine nucleotides (NAD and ATP) on spontaneous arrhythmogenic activity caused by norepinephrine in myocardial sleeves of pulmonary veins. In pulmonary veins, NAD and ATP reduced the frequency of action potentials and their duration at regular type of spontaneous activity caused by norepinephrine. NAD and ATP lengthened the intervals between spike bursts at periodic (burst) type of spontaneous activity.

Effects of exogenous nicotinamide adenine dinucleotide (NAD+) in the rat heart are mediated by P2 purine receptors.

Background: Recently, NAD+ has been considered as an essential factor, participating in nerve control of physiological functions and intercellular communication. NAD+ also has been supposed as endogenous activator of P1 and P2 purinoreceptors. Effects of extracellular NAD+ remain poorly investigated in cardiac tissue.

Effects of Nicotinamide Adenine Dinucleotide (NAD(+)) and Diadenosine Tetraphosphate (Ap4A) on Electrical Activity of Working and Pacemaker Atrial Myocardium in Guinea Pigs.

Effects of nucleotide polyphosphate compounds (nicotinamide adenine dinucleotide, NAD(+); diadenosine tetraphosphate, Ap4A) on the confi guration of action potentials were studied in isolated preparations of guinea pig sinoatrial node and right atrial appendage (auricle). In the working myocardium, NAD(+) and Ap4A in concentrations of 10(-5) and 10(-4) M had no effect on resting potential, but significantly reduced the duration of action potentials; the most pronounced decrease was found at 25% repolarization. In the primary pacemaker of the sinoatrial node, both concentrations of NAD(+) and Ap4A induced hyperpolarization and reduction in the rate of slow diastolic depolarization, but significant slowing of the sinus rhythm was produced by these substances only in the concentration of 10(-4) M.

Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors.

Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated.

Effect of Exogenous Extracellular Nicotinamide Adenine Dinucleotide (NAD⁺) on Bioelectric Activity of the Pacemaker and Conduction System of the Heart.

In rat sinoatrial node, NAD(+) (10 μM) reduced the rate of spontaneous action potentials, duration of action potentials, and the velocity of slow diastolic depolarization, but the rate of action potential front propagation increases. In passed rabbit Purkinje fibers, NAD(+) (10 μM) reduced the duration of action potentials. Under conditions of spontaneous activity of Purkinje fibers, NAD(+) reduced the fi ring rate and the rate of slow diastolic depolarization.

[Influence exogenous nicotinamide adenine dinucleotide (NAD+) on contractile and bioelectric activity of the rat heart].

This study is aimed to the investigation of the nicotinamide adenine dinucleotide (NAD+) effects and mechanisms of action in a heart. NAD+ (mcM) induces multiphase alternation of contractile activity of isolated rat heart: short positive inotropic action is followed by a negative inotropic phase. NAD+ (1-100 mcM) induces decreasing of action potential duration (APD) in rat atrial myocardium (from 45 +/- 0.