A5015213442- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Atrial Fibrillation Management and Outcomes
- Cardiac Arrhythmias and Treatments
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Cardiovascular Function and Risk Factors
- Caveolin-1 and cellular processes
- Cardiac Arrest and Resuscitation
- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- ECG Monitoring and Analysis
- Oral and gingival health research
- Genetic Syndromes and Imprinting
- Diet, Metabolism, and Disease
- Cardiac Imaging and Diagnostics
- Cardiac Ischemia and Reperfusion
- Cardiac pacing and defibrillation studies
- Cardiovascular Disease and Adiposity
Lundbeck (Denmark)
2019-2020
University of Copenhagen
2011-2018
Acesion Pharma (Denmark)
2017
Rigshospitalet
2011-2017
Danish National Research Foundation
2011-2015
Stellenbosch University
2013
Statens Serum Institut
2013
St George's Hospital
2013
St George's, University of London
2013
University College Hospital at Westmoreland Street
2013
AimsSmall-conductance calcium-activated potassium (SK) channels are expressed in the heart of various species, including humans. The aim present study was to address whether SK play a functional role human atria.
We have shown previously that inhibition of small conductance Ca(2+)-activated K(+) (SK) channels is antiarrhythmic in models acutely induced atrial fibrillation (AF). These models, however, do not take into account AF derives from a wide range predisposing factors, the most prevalent being hypertension. In this study we assessed effects two different SK channel inhibitors, NS8593 and UCL1684, aging, spontaneously hypertensive rats to examine their properties setting hypertension-induced...
Atrial fibrillation (AF) is associated with increased morbidity and in addition the most prevalent cardiac arrhythmia. Compounds used pharmacological treatment has traditionally been divided into Na+ channel inhibitors, β-blockers, K+ Ca2+ whereas newer multichannel blockers such as amiodarone ranolazine have introduced later. This study was devoted to evaluation of an acute pacing-induced vivo model AF rats. Antiarrhythmic effects well-known compounds lidocaine, dofetilide, were confirmed...
Evidence has emerged that small-conductance Ca2+-activated K+ (SK) channels constitute a new target for treatment of atrial fibrillation (AF). SK are predominantly expressed in the atria as compared with ventricles. Various marketed antiarrhythmic drugs limited by ventricular adverse effects and efficacy loss AF progresses.A total 43 pigs were used studies. reversion conscious long-term tachypaced pigs: Pigs subjected to tachypacing (7 Hz) until they developed sustained could not be reverted...
Familial growth hormone deficiency provides an opportunity to identify new genetic causes of short stature. Here we combine linkage analysis with whole-genome resequencing in patients and maternally inherited gingival fibromatosis. We report that from three unrelated families harbor either two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), KCNQ1, a gene previously implicated the long QT interval syndrome. Kcnq1 is expressed hypothalamic GHRH neurons pituitary...
AimsThe purpose of this study was to investigate the functional role G-protein-coupled inward rectifier potassium (GIRK) channels in cardiac ventricle.
The voltage-gated Kv1.5 potassium channel, conducting the ultra-rapid rectifier K(+) current (IKur), is regulated through several pathways. Here we investigate if surface expression controlled by 2 kinases PKC and AMPK, using Xenopus oocytes, MDCK cells atrial derived HL-1 cells. By confocal microscopy combined with electrophysiology demonstrate that activation reduces current, a decrease in membrane expressed channels. AMPK was found to cells, but not furthermore shown be dependent on...
Mutations in CAV3, coding for caveolin-3, the major constituent scaffolding protein of cardiac caveolae, have been associated with skeletal muscle disease, cardiomyopathy, and most recently long-QT syndrome (LQTS) sudden infant death syndrome. We examined occurrence CAV3 mutations a large cohort patients LQTS.Probands LQTS (n=167) were screened using direct DNA sequencing. A single proband (0.6%) was found to be heterozygous carrier previously described missense mutation, caveolin-3:p.T78M....
Introduction: SK channels have functional importance in the cardiac atrium of many species, including humans. Pharmacological blockage has been reported to be antiarrhythmic animal models atrial fibrillation; however, exact mechanism channel inhibition remains unclear. Objectives: We speculated that together with a direct repolarizing current, previously observed depolarization resting membrane potential (RMP) after reduces sodium availability, thereby prolonging effective refractory period...
G protein-coupled inwardly rectifying K⁺ channels (GIRK) are important in the regulation of heart rate and atrial electrophysiology. GIRK activated by receptors, including muscarinic M₂ receptors adenosine A₁ receptors. The aim this study was to characterize compare electrophysiological effects acetylcholine (ACh) on rat atria. Action potential duration at 90% repolarization (APD₉₀), effective refractory period (ERP), resting membrane (RMP) were investigated isolated atria intracellular...
Sympathetic and vagal activation is linked to atrial arrhythmogenesis. Here we investigated the small conductance Ca2+-activated K+ (SK)-channel pore-blocker N-(pyridin-2-yl)-4-(pyridine-2-yl)thiazol-2-amine (ICA) on action potential (AP) fibrillation (AF) parameters in isolated rat atria during β-adrenergic [isoprenaline (ISO)] muscarinic M2 [carbachol (CCh)] activation. Furthermore, antiarrhythmic efficacy of ICA was benchmarked toward class-IC drug flecainide (Fleca). ISO increased...
Ventricular fibrillation (VF) occurring in the first minutes to hours of acute myocardial infarction (AMI) is a frequent cause death and treatment options are limited. The aim was test whether early infusion amiodarone 10 min after onset AMI reduced incidence VF porcine model. Eighteen female Danish landrace pigs were randomized control an group. induced by ligation mid-left anterior descending artery for 120 followed 60 reperfusion. occurred 0/8 treated with compared 7/10 controls (P <...
Over the last years extensive kinase-mediated regulation of a number voltage-gated potassium (Kv) channels important in cardiac electrophysiology has been reported. This includes Kv1.5, Kv7.1 and Kv11.1 cell surface expression, where appears to center around ubiquitin ligase Nedd4-2. In present study we examined whether Kv1.4, constituting Ito,s current, is subject similar regulation. epithelial Madin-Darby Canine Kidney (MDCK) line, which constitutes highly reproducible model system for...
Background. Congenital long QT syndrome (LQTS) is a hereditary cardiac channelopathy characterized by delayed ventricular repolarization, syncope, torsades de pointes and sudden death. Thirty-three members of five apparently ‘unrelated’ Danish families carry the KCNH2:c.87C> A; p.F29L founder mutation. Methods Results. Linkage disequilibrium mapping with microsatellites around KCNH2 enabled us to estimate age mutation be approximately 22 generations, corresponding 550 years....
The inwardly rectifying potassium current (IK 1) conducted through Kir2.X channels contribute to repolarization of the cardiac action potential and stabilization resting membrane in cardiomyocytes. Our aim was investigate effect recently discovered IK 1 inhibitor PA-6 on refractoriness isolated rat hearts. Transiently transfected HEK-293 cells expressing were voltage-clamped with ramp protocols. Langendorff-perfused heart experiments performed male Sprague-Dawley rats, effective refractory...
Although several physiological, pathophysiological and regulatory properties of classical inward rectifier K+ current I(K1), G-protein coupled inwardly-rectifying I(K,ACh) the small-conductance Ca2+ activated I(K,Ca) have been identified, quantitative biophysical details remain unclear. Both I(K1) are implicated in atrial fibrillation (AF), recently also has speculated to be linked with genesis sustainability AF. All these three currents shown involved electrical remodeling atria patients...
Purpose: The aim of the present study was to investigate electrical activity cardiac tissue in rat SVC and AZV.Materials methods: Electrically evoked or spontaneous action potentials (AP) resting membrane potential (RPM) were recorded multicellular isolated Tirode perfused preparations left right atria (LA, RA), AZV with use standard microelectrode technique control conditions under application noradrenaline (NA, 10 lM), isoproterenol (ISO, lM) phenylephrine (PHE, lM).All dissected from...