A5039588653- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiac Arrhythmias and Treatments
- Atrial Fibrillation Management and Outcomes
- Cardiac Imaging and Diagnostics
- Cardiovascular Function and Risk Factors
- Receptor Mechanisms and Signaling
- Cardiac pacing and defibrillation studies
- Cardiovascular Effects of Exercise
- Neuroscience and Neuropharmacology Research
- Obstructive Sleep Apnea Research
- Neuroscience and Neural Engineering
- Cardiomyopathy and Myosin Studies
- Cardiac Ischemia and Reperfusion
- ECG Monitoring and Analysis
- Cardiovascular Disease and Adiposity
- Cardiac Valve Diseases and Treatments
- Cardiac Arrest and Resuscitation
- Neuroscience of respiration and sleep
- Diabetes Treatment and Management
- Virus-based gene therapy research
- Acute Myocardial Infarction Research
- Heart Rate Variability and Autonomic Control
- Ion Transport and Channel Regulation
- Adenosine and Purinergic Signaling
University of Copenhagen
2016-2025
Ørsted (Denmark)
2025
Gentofte Hospital
2019-2021
Frederiksberg Hospital
2020
Center for Clinical Research and Prevention
2020
Rigshospitalet
2011-2019
Danish National Research Foundation
2008-2018
University of Colorado Anschutz Medical Campus
2018
Halliburton (United Kingdom)
2018
Statens Serum Institut
2012-2017
Background and aim The potential of microRNAs (miRNA) as non-invasive diagnostic, prognostic, predictive biomarkers, well therapeutic targets, has recently been recognized. Previous studies have highlighted the importance consistency in methodology used, but to our knowledge, no study described sample preparation storage systematically with respect miRNAs blood biomarkers. this was investigate stability under various relevant clinical research conditions: different collection tubes, at...
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.
Background— Recently, evidence has emerged that small-conductance Ca 2+ -activated K + (SK) channels are predominantly expressed in the atria a number of species including human. In rat, guinea pig, and rabbit ex vivo models atrial fibrillation (AF), we used 3 different SK channel inhibitors, UCL1684, N -(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA), NS8593, to assess hypothesis pharmacological inhibition is antiarrhythmic. Methods Results— isolated, perfused pig hearts, AF could be...
Background— Atrial fibrillation (AF) is the most common cardiac arrhythmia. The sodium channel, Na V 1.5, plays a pivotal role in setting conduction velocity and initial depolarization of myocytes. We hypothesized that early-onset lone AF was associated with genetic variation SCN5A . Methods Results— coding sequence sequenced 192 patients AF. Eight nonsynonymous mutations (T220I, R340Q, T1304M, F1596I, R1626H, D1819N, R1897W, V1951M) 2 rare variants (S216L F2004L) were identified. Of 11...
Small-conductance Ca2+-activated K+ (SK)-channel inhibitors have antiarrhythmic effects in animal models of atrial fibrillation (AF), presenting a potential novel option. However, the regulation SK-channels human cardiomyocytes and its modification patients with AF are poorly understood were object this study. Apamin-sensitive SK-channel current (ISK) action potentials recorded right-atrial from sinus rhythm control (Ctl) or (long-standing persistent) chronic (cAF). ISK was significantly...
Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated increased heart rate, the mechanism of which unclear. Methods results We employed a large animal model, female landrace pig, multiple in vivo ex approaches including pharmacological challenges, electrophysiology, high-resolution mass spectrometry explore how elicits an increase...
KCNE4 is a membrane protein belonging to family of single transmembrane domain proteins known have dramatic effect on the gating certain potassium channels. However, no functional role has been suggested so far. In present paper we demonstrate that an inhibitory subunit KCNQ1 Co‐expression and in Xenopus oocytes completely inhibited current. This was reproduced mammalian CHO‐K1 cells. Experiments with delayed expression mRNA coding for KCNQ1‐expressing exerts its channels already expressed...
Both Xenopus laevis oocytes and mammalian cells are widely used for heterologous expression of several classes proteins, membrane proteins especially, such as ion channels or receptors, have been extensively investigated in both cell types. A full characterization a specific protein will often engage cells. Efficient systems thus far only possible by subcloning the cDNA into two different vectors because molecular requirements should be fulfilled to obtain high level oocytes. To address this...
Objective: The voltage-gated KCNQ1 potassium channel regulates key physiological functions in a number of tissues. In the heart, α-subunits assemble with KCNE1 β-subunits forming complex constituting delayed rectifier current IKs. epithelia, channels participate controlling body electrolyte homeostasis. Several regulatory mechanisms complexes have been reported, including protein kinase A (PKA)-phosphorylation and β-subunit interactions. However, membrane density attracted less attention.
The voltage-gated Na + channels (Na v ) form a family composed of 10 genes. COOH termini contain cluster amino acids that are nearly identical among 7 the members. This COOH-terminal sequence, PPSYDSV, is PY motif known to bind WW domains E3 protein-ubiquitin ligases Nedd4 family. We recently reported cardiac 1.5 regulated by Nedd4-2. In this study, we further investigated molecular determinants regulation proteins. When expressed in HEK-293 cells and studied using whole cell voltage...
Atrial fibrillation (AF) is the most frequent arrhythmia. Screening of SCN5A-the gene encoding α-subunit cardiac sodium channel-has indicated that disturbances current may play a central role in mechanism lone AF. We tested hypothesis AF young patients associated with genetic mutations SCN3B and SCN4B, genes two β-subunits channel.In 192 unrelated patients, entire coding sequence splice junctions SCN4B were bidirectionally sequenced. Three non-synonymous found (R6K, L10P, M161T). Two novel...
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...
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...
Background— Genome-wide association studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A , encoding voltage-gated Na v 1.8 sodium channel, is associated with PR-interval prolongation and atrial fibrillation (AF). Single high linkage disequilibrium nonsynonymous variant rs6795970 (V1073A, r 2 =0.933). We therefore sought to determine whether rare variants are early onset AF. Methods Results— was sequenced 225 AF patients whom there no evidence of other...
Slowly inactivating Na+ channels conducting "late" current (INa,late) contribute to ventricular arrhythmogenesis under pathological conditions. INa,late was also reported play a role in chronic atrial fibrillation (AF). The objective of this study investigate human right cardiomyocytes as putative drug target for treatment AF. To activate channels, from transgenic mice which exhibit (ΔKPQ), and patients sinus rhythm (SR) AF were voltage clamped at room temperature by 250-ms long test pulses...