Gaborit, Nathalie, Wichter, Thomas, Varro, Andras, Szuts, Viktoria, Lamirault, Guillaume, Eckardt, Lars, ...
Aims Brugada syndrome is an inherited sudden-death arrhythmia syndrome. Na+-current dysfunction is central, but mutations in the SCN5A gene (encoding the cardiac Na+-channel Nav1.5) are present in...
Kirchhof, Paulus, Bax, Jeroen, Blomstrom-Lundquist, Carina, Calkins, Hugh, Camm, A. John, Cappato, Ricardo, ...
Shiroshita-Takeshita, Akiko, Mitamura, Hideo, Ogawa, Satoshi, Nattel, Stanley
Aims Although atrial-tachycardia remodelling is a significant atrial fibrillation (AF) promoting factor, little information is available about how atrial-tachycardia rate determines remodelling...
Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis (2009)
Michael, Georghia, Xiao, Ling, Qi, Xiao-Yan, Dobrev, Dobromir, Nattel, Stanley
Cardiac action potentials (APs) are driven by ionic currents flowing through specific channels and exchangers across cardiomyocyte membranes. Once initiated by rapid Na+ entry during phase 0, the AP...
S Nattel, W Jing, Stanley Nattel, Wuhua Jing
Rate-dependent changes in intraventricular conduction produced by procainamide in anesthetized dogs. A quantitative analysis based on the relation between phase 0
Diness, Thomas G., Yeh, Yung-Hsin, Qi, Xiao Yan, Chartier, Denis, Tsuji, Yukiomi, Hansen, Rie S., ...
Aims Impaired repolarization in cardiac myocytes can lead to long QT syndrome (LQTS), with delayed repolarization and increased susceptibility to Torsades de Pointes (TdP) arrhythmias. Current...
Voigt, Niels, Maguy, Ange, Yeh, Yung-Hsin, Qi, Xiaoyan, Ravens, Ursula, Dobrev, Dobromir, ...
Aims Although atrial tachycardia (AT) remodelling promotes agonist-independent, constitutively active, acetylcholine-regulated K+-current (IK,ACh) that increases susceptibility to atrial fibrillation...
Heat shock proteins as molecular targets for intervention in atrial fibrillation (2008)
Ke, Lei, Dijkhuis, Anne-Jan, Qi, XiaoYan, Shiroshita-Takeshita, Akiko, Nattel, Stanley, ...
Atrial fibrillation (AF) is the most common sustained clinical tachyarrhythmia. AF is a progressive condition as demonstrated by the finding that maintenance of normal rhythm and contractile function...
Sakabe, Masao, Shiroshita-Takeshita, Akiko, Maguy, Ange, Fujiki, Akira, Inoue, Hiroshi, ...
Aims Heat shock proteins (HSPs) are a set of endogenous cytoprotective factors activated by various pathological conditions. This study addressed the effects of geranylgeranylacetone (GGA), an orally...
Shimano, Masayuki, Tsuji, Yukiomi, Yoshida, Yukihiko, Inden, Yasuya, Tsuboi, Naoya, Itoh, Teruo, ...
Aims We assessed the effects of cardiac re-synchronization therapy (CRT) in patients who developed otherwise unexplained heart failure (HF) during right ventricular apical (RVA)-pacing for acquired...
Characterization of the cardiac KCNE1 gene promoter (2007)
Mustapha, Zenab, Pang, Li, Nattel, Stanley
Background: KCNE1 encodes an essential cardiac slow delayed-rectifier potassium current (IKs) β-subunit (minK). Varying minK expression is important in disease-related remodeling and...
Yeh, Yung-Hsin, Ehrlich, Joachim R., Qi, Xiaoyan, Hébert, Terence E., Chartier, Denis, Nattel, Stanley
Objectives: Canine atrial cardiomyocytes display a constitutively active, acetylcholine-regulated, time-dependent K+ current (IKH) that contributes to atrial repolarization and atrial...
Voigt, Niels, Maguy, Ange, Yeh, Yung-Hsin, Qi, Xiaoyan, Ravens, Ursula, Dobrev, Dobromir, ...
Aims Although atrial tachycardia (AT) remodelling promotes agonist-independent, constitutively active, acetylcholine-regulated K+-current (IK,ACh) that increases susceptibility to atrial fibrillation...
Voigt, Niels, Maguy, Ange, Yeh, Yung-Hsin, Qi, Xiaoyan, Ravens, Ursula, Dobrev, Dobromir, ...
Aims Although atrial tachycardia (AT) remodelling promotes agonist-independent, constitutively active, acetylcholine-regulated K+-current (IK,ACh) that increases susceptibility to atrial fibrillation...
Burstein, Brett, Qi, Xiao-Yan, Yeh, Yung-Hsin, Calderone, Angelino, Nattel, Stanley
Objective Atrial fibrillation (AF) causes tachycardia-induced atrial electrical remodeling, contributing to the progressive nature of the arrhythmia. Ventricular dysfunction due to a rapid response...
Rivard, Lena, Sinno, Hani, Shiroshita-Takeshita, Akiko, Schram, Gernot, Leung, Tack-Ki, Nattel, Stanley
Objective: Acute atrial ischemia produces a substrate for atrial fibrillation (AF) maintenance, but the response of this substrate to antiarrhythmic-drugs has not been defined. The present study...
Shiroshita-Takeshita, Akiko, Burstein, Brett, Leung, Tack-Ki, Mitamura, Hideo, Ogawa, Satoshi, ...
Background: Congestive heart failure (CHF) is a common cause of atrial fibrillation (AF). Oxidative stress and inflammation (profibrotic) and peroxisome proliferator-activated receptor- (PPAR-,...
Ehrlich, Joachim R., Hohnloser, Stefan H., Nattel, Stanley
Atrial fibrillation (AF) is a common arrhythmia that is difficult to treat. Anti-arrhythmic drug therapy, to maintain sinus-rhythm, is limited by inadequate efficacy and potentially serious adverse...
White, Donald E., Coutu, Pierre, Shi, Yan-Fen, Tardif, Jean-Claude, Nattel, Stanley, St. Arnaud, René, ...
A requirement for integrin-mediated adhesion in cardiac physiology is revealed through targeted deletion of inte-grin-associated genes in the murine heart. Here we show that targeted ablation of the...
Involvement of lipid rafts and caveolae in cardiac ion channel function (2006)
Maguy, Ange, Hebert, Terence E., Nattel, Stanley
A variety of lipid microdomains, including caveolae, have been shown to play an important role in both protein targetting and in controlling protein–protein interactions. There is increasing...
Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs (2006)
Shiroshita-Takeshita, Akiko, Lavoie, Joel, Nattel, Stanley
Background: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the...
Melnyk, Peter, Ehrlich, Joachim R., Pourrier, Marc, Villeneuve, Louis, Cha, Tae-Joon, Nattel, Stanley
Background: Cardiomyocytes in pulmonary vein (PV) sleeves are important in atrial fibrillation (AF), but underlying mechanisms are poorly understood. Pulmonary veins have different ionic current...
Ehrlich, Joachim R., Zicha, Stephen, Coutu, Pierre, Hébert, Terence E., Nattel, Stanley
Background: Atrial fibrillation (AF) is a common acquired arrhythmia with multi-factorial pathogenesis. Recently, a single nucleotide polymorphism (SNP, A/G) at position 112 in the KCNE1 gene,...
Ehrlich, Joachim R., Hohnloser, Stefan H., Nattel, Stanley
Atrial fibrillation (AF) is a common arrhythmia that is difficult to treat. Anti-arrhythmic drug therapy, to maintain sinus-rhythm, is limited by inadequate efficacy and potentially serious adverse...
Zicha, Stephen, Fernández-Velasco, María, Lonardo, Giuseppe, L'Heureux, Nathalie, Nattel, Stanley
Background: The hyperpolarization-activated cation current If contributes significantly to sinoatrial node pacemaker function and possibly to ectopic arrhythmogenesis. Little is known about the...
Hanna, Nessrine, Cardin, Sophie, Leung, Tack-Ki, Nattel, Stanley
Background: Congestive heart failure (CHF) causes arrhythmogenic remodeling in both atria and ventricles, but differences between atrial and ventricular remodeling in CHF have not been well...
Nakashima, Hideko, Gerlach, Uwe, Schmidt, Dietmar, Nattel, Stanley
Objectives: This study evaluated the in vivo electrophysiological effects of a highly selective slow delayed-rectifier K+-current blocker, HMR 1556, to gain insights into the consequences of...
Cardin, Sophie, Li, Danshi, Thorin-Trescases, Nathalie, Leung, Tack-Ki, Thorin, Eric, Nattel, Stanley
Objective: Augmented atrial apoptosis, angiotensin II expression, and related signalling pathway activation have been shown in clinical atrial fibrillation (AF), but their significance is poorly...
Schram, Gernot, Pourrier, Marc, Wang, Zhiguo, White, Michel, Nattel, Stanley
Background: Kir2 subunits are believed to underlie the cardiac inwardly rectifying current IK1. The subunit composition of native IK1 currents is uncertain, and it has been suggested that...
Atrial fibrillation (AF) is a very common clinical problem, and presently available treatment options are suboptimal. A tremendous amount has been learned over the past 10 years about the atrial...
Kneller, James, Sun, Hui, Leblanc, Normand, Nattel, Stanley
Background: Loss of rate-dependent action potential (AP) duration (APD) adaptation is a characteristic feature of atrial tachycardia-induced remodeling (ATR). ATR causes sarcolemmal ion-channel...
Shinagawa, Kaori, Mitamura, Hideo, Ogawa, Satoshi, Nattel, Stanley
Background: Inhibitors of the Na+/H+-exchanger (NHE1) and of angiotensin-converting enzyme (ACE) have been shown to reduce short-term (
Shi, Yanfen, Li, Danshi, Tardif, Jean-Claude, Nattel, Stanley
Objective: Atrial remodeling contributes to the maintenance of atrial fibrillation (AF) in several cardiac disorders. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce the...
Sun, Hui, Chartier, Denis, Leblanc, Normand, Nattel, Stanley
Objectives: Indirect evidence suggests a role for Ca2+-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca2+]...
Fareh, Samir, Bénardeau, Agnès, Nattel, Stanley
Background: Tachycardia-induced remodeling likely plays an important role in atrial fibrillation (AF) maintenance and recurrence after cardioversion, and Ca2+ overload may be an important mediator....
Derakhchan, Katayoun, Villemaire, Christine, Talajic, Mario, Nattel, Stanley
Background: Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of...
Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs (2001)
Bénardeau, Agnès, Fareh, Samir, Nattel, Stanley
Background: Atrial tachycardia-induced remodeling promotes the occurrence and maintenance of atrial fibrillation (AF) and decreases L-type Ca2+ current. There is also a clinical suggestion that acute...
Remodeling of atrial dimensions and emptying function in canine models of atrial fibrillation (2001)
Shi, Yanfen, Ducharme, Anique, Li, Danshi, Gaspo, Rania, Nattel, Stanley, Tardif, Jean-Claude
Objectives: Atrial tachycardia-induced remodeling (ATR) and ventricular tachypacing-induced heart failure (HF) create experimental substrates for atrial fibrillation (AF), and both have been reported...
Yue, Lixia, Feng, Jian Lin, Wang, Zhiguo, Nattel, Stanley
Objective: A dog atrial ultra-rapid delayed rectifier current (IKur.d) is involved in canine atrial repolarization and shares similarities with the human atrial ultra-rapid delayed rectifier (IKur)....
One of the most exciting developments in our understanding of atrial fibrillation (AF) over the last several years has been the recognition that AF itself modifies atrial electrical properties in a...
Gaspo, Rania, Sun, Hui, Fareh, Samir, Levi, Mirie, Yue, Lixia, Allen, Bruce G., ...
Background: We have shown that rapid atrial activation, as occurs during atrial fibrillation (AF), reduces L-type Ca2+ current (ICa) and that this is the principal mechanism of the action potential...
Courtemanche, Marc, Ramirez, Rafael J, Nattel, Stanley
Recent advances in molecular electrophysiology have made possible the development of more selective ion channel blockers for therapeutic use. However, more information is needed about the effects of...
Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs (1998)
The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or proarrhythmia. This complication may be lethal, and greatly restricts the value of antiarrhythmic...
Nattel, Stanley, Liu, Lili, St-Georges, Dalie
Objectives: This study was designed to evaluate how the atrial electrophysiological and antiarrhythmic effects of azimilide compare with those of the specific rapid delayed rectifier (IKr) blocker...
Rapid and slow components of delayed rectifier current in human atrial myocytes (1994)
Wang, Zhiguo, Fermini, Bernard, Nattel, Stanley
Objective: Previous studies in guinea pig heart cells have shown pharmacologically and kinetically distinct components of the classical delayed rectifier current (IK), generally referred to as IKr...
Rousseau, Guy, St-Jean, Gilles, Latour, Jean-Gilles, Merhi, Yahye, Nattel, Stanley, Waters, David
Study objective – The aim was to demonstrate the ability of diltiazem to protect the ischaemic myocardium in the course of coronary reperfusion, and to establish if an interaction with neutrophils...
NAYEBPOUR, MOHSEN, SOLYMOSS, B CHARLES, NATTEL, STANLEY
Caesium chloride administration has been used in an animal model to reproduce the acquired long QT syndrome observed in man, but the transient nature of the arrhythmogenic action of caesium has made...
NATTEL, STANLEY, QUANTZ, MACKENZIE A
The purpose of these experiments was to study the pharmacological response of quinidine induced early afterdepolarisations to gain insights into underlying ionic mechanisms. Quinidine (8.5 µM)...
Effect of frequent ventricular ectopy on myocardial infarct size in dogs (1987)
NATTEL, STANLEY, BEAU, SCOTT, McCARRAGHER, GARY
Tachycardia is known to increase the size of an evolving myocardial infarction, but the effect of frequent ventricular extrasystoles on infarct size is unknown. To determine the effect dogs were...
NATTEL, STANLEY, PEDERSEN, DONAL H, ZIPES, DOUGLAS P
Little information exists regarding the effects of coronary artery occlusion on the distribution and actions of antiarrhythmic agents. We administered aprindine to dogs before, 5 min after, and 24 h...
New insights into the mechanisms and management of atrial fibrillation
ATRIAL FIBRILLATION (AF) IS A COMMON CONTRIBUTOR to cardiovascular morbidity and mortality. Two generally acceptable strategies exist for long-term AF management, with ongoing studies comparing the...
Pandit, Sandeep V., Berenfeld, Omer, Anumonwo, Justus M. B., Zaritski, Roman M., Kneller, James, Nattel, Stanley, ...
Recent studies suggest that atrial fibrillation (AF) is maintained by fibrillatory conduction emanating from a small number of high-frequency reentrant sources (rotors). Our goal was to study the...
Zicha, Stephen, Xiao, Ling, Stafford, Sara, Cha, Tae Joon, Han, Wei, Varro, Andras, ...
The transient outward current (Ito), an important contributor to transmural electrophysiological heterogeneity, is significantly remodelled in congestive heart failure (CHF). The molecular bases of...
Liu, Gong Xin, Zhou, Jun, Nattel, Stanley, Koren, Gideon
The rapidly delayed rectifier current (IKr) has been described in ventricular myocytes isolated from many species, as well as from neonatal mice. However, whether IKr is present in the adult mouse...
Ehrlich, Joachim R, Cha, Tae-Joon, Zhang, Liming, Chartier, Denis, Villeneuve, Louis, Hébert, Terence E, ...
Cardiomyocytes from the pulmonary vein sleeves (PVs) are known to play an important role in atrial fibrillation. PVs have been shown to exhibit time-dependent hyperpolarization-induced inward...
New insights into the mechanisms and management of atrial fibrillation
ATRIAL FIBRILLATION (AF) IS A COMMON CONTRIBUTOR to cardiovascular morbidity and mortality. Two generally acceptable strategies exist for long-term AF management, with ongoing studies comparing the...
Pandit, Sandeep V., Berenfeld, Omer, Anumonwo, Justus M. B., Zaritski, Roman M., Kneller, James, Nattel, Stanley, ...
Recent studies suggest that atrial fibrillation (AF) is maintained by fibrillatory conduction emanating from a small number of high-frequency reentrant sources (rotors). Our goal was to study the...
Liu, Gong Xin, Zhou, Jun, Nattel, Stanley, Koren, Gideon
The rapidly delayed rectifier current (IKr) has been described in ventricular myocytes isolated from many species, as well as from neonatal mice. However, whether IKr is present in the adult mouse...
Ehrlich, Joachim R, Cha, Tae-Joon, Zhang, Liming, Chartier, Denis, Villeneuve, Louis, Hébert, Terence E, ...
Cardiomyocytes from the pulmonary vein sleeves (PVs) are known to play an important role in atrial fibrillation. PVs have been shown to exhibit time-dependent hyperpolarization-induced inward...
Zicha, Stephen, Xiao, Ling, Stafford, Sara, Cha, Tae Joon, Han, Wei, Varro, Andras, ...
The transient outward current (Ito), an important contributor to transmural electrophysiological heterogeneity, is significantly remodelled in congestive heart failure (CHF). The molecular bases of...
White, Donald E., Coutu, Pierre, Shi, Yan-Fen, Tardif, Jean-Claude, Nattel, Stanley, Arnaud, RenéSt., ...
A requirement for integrin-mediated adhesion in cardiac physiology is revealed through targeted deletion of inte-grin-associated genes in the murine heart. Here we show that targeted ablation of the...
Effects of flecainide and quinidine on Kv4.2 currents: voltage dependence and role of S6 valines
Caballero, Ricardo, Pourrier, Marc, Schram, Gernot, Delpón, Eva, Tamargo, Juan, Nattel, Stanley
The effects of flecainide and quinidine were studied on wild-type Kv4.2 channels (Kv4.2WT), channels with deletion of the N-terminal domain (N-del) and channels with mutations in the valine residues...
Potential mechanisms for the enhancement of HERG K+ channel function by phospholipid metabolites
Wang, Jingxiong, Zhang, Yiqiang, Wang, Huizhen, Han, Hong, Nattel, Stanley, Yang, Baofeng, ...
Phospholipid metabolites lysophospholipids cause extracellular K+ accumulation and action potential shortening with increased risk of arrhythmias during myocardial ischemia. Here we studied effects...
Ranolazine: Ion-channel-blocking actions and in vivo electrophysiological effects
Schram, Gernot, Zhang, Liming, Derakhchan, Katayoun, Ehrlich, Joachim R, Belardinelli, Luiz, Nattel, Stanley
Ranolazine is a novel anti-ischemic drug that prolongs the QT interval. To evaluate the potential mechanisms and consequences, we studied: (i) Ranolazine's effects on HERG and IsK currents in Xenopus...
The Treatment of PVCs and Prevention of Sudden Cardiac Death: New findings from the CAST study
Premature ventricular complexes (PVCs) have traditionally been suppressed using antiarrhythmic drugs. Recent studies have failed to show that reducing the number of PVCs can prevent sudden death;...
Adrenergic control of the ultrarapid delayed rectifier current in canine atrial myocytes
Yue, Lixia, Feng, Jianlin, Wang, Zhiguo, Nattel, Stanley
The effects of adrenergic stimulation on the ultrarapid delayed rectifier K+ current (IKur,d) of dog atrial myocytes was studied with patch-clamp methods.Isoproterenol (isoprenaline) increased IKur,d...
Weerapura, Manjula, Nattel, Stanley, Courtemanche, Marc, Doern, David, Ethier, Nathalie, Hébert, Terence E
The effects of Ba2+ on current resulting from the heterologous expression of the human ether-à-go-go related gene (HERG) (IHERG) was studied with two-electrode voltage clamp techniques in Xenopus...
Yue, Lixia, Wang, Zhiguo, Rindt, Hansjorg, Nattel, Stanley
We previously described an ultrarapid delayed rectifier current in dog atrial myocytes (IKur,d) with properties resembling currents reported for Kv3.1 channels in neural tissue; however, there was no...
Weerapura, Manjula, Nattel, Stanley, Chartier, Denis, Caballero, Ricardo, Hébert, Terence E
Although it has been suggested that coexpression of minK related peptide (MiRP1) is required for reconstitution of native rapid delayed-rectifier current (IKr) by human ether-a-go-go related gene...
Schram, Gernot, Melnyk, Peter, Pourrier, Marc, Wang, Zhiguo, Nattel, Stanley
Heteromeric channel assembly is a potential source of physiological variability. The potential significance of Kir2 subunit heterotetramerization has been controversial, but recent findings suggest...
Ehrlich, Joachim R, Cha, Tae-Joon, Zhang, Liming, Chartier, Denis, Melnyk, Peter, Hohnloser, Stefan H, ...
Pulmonary vein (PV) cardiomyocytes play an important role in atrial fibrillation; however, little is known about their specific cellular electrophysiological properties. We applied standard...
Gaborit, Nathalie, Le Bouter, Sabrina, Szuts, Viktoria, Varro, Andras, Escande, Denis, Nattel, Stanley, ...
The various cardiac regions have specific action potential properties appropriate to their electrical specialization, resulting from a specific pattern of ion-channel functional expression. The...
Abi-Char, Joëlle, Maguy, Ange, Coulombe, Alain, Balse, Elise, Ratajczak, Philippe, Samuel, Jane-Lise, ...
Membrane lipid composition is a major determinant of cell excitability. In this study, we assessed the role of membrane cholesterol composition in the distribution and function of Kv1.5-based...
Differential Interactions of Na+ Channel Toxins with T-type Ca2+ Channels
Sun, Hui, Varela, Diego, Chartier, Denis, Ruben, Peter C., Nattel, Stanley, Zamponi, Gerald W., ...
Two types of voltage-dependent Ca2+ channels have been identified in heart: high (ICaL) and low (ICaT) voltage-activated Ca2+ channels. In guinea pig ventricular myocytes, low voltage–activated...