A5071825449- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Cardiac Arrhythmias and Treatments
- Nicotinic Acetylcholine Receptors Study
- Atrial Fibrillation Management and Outcomes
- Neuroscience and Neural Engineering
- Cardiac Ischemia and Reperfusion
- Cardiac pacing and defibrillation studies
- Cardiovascular Effects of Exercise
- Ion Transport and Channel Regulation
- Cardiomyopathy and Myosin Studies
- Mitochondrial Function and Pathology
- Neural dynamics and brain function
- Coordination Chemistry and Organometallics
- Genetic Neurodegenerative Diseases
- ECG Monitoring and Analysis
- Pain Mechanisms and Treatments
- Blood Pressure and Hypertension Studies
- Neurological disorders and treatments
- Renin-Angiotensin System Studies
- Photoreceptor and optogenetics research
- Ion Channels and Receptors
- Electrochemical Analysis and Applications
Acesion Pharma (Denmark)
2013-2023
Lundbeck (Denmark)
2013-2020
University of Copenhagen
2009-2018
Rigshospitalet
2011-2017
Danish National Research Foundation
2006-2015
NeuroSearch (Denmark)
2005-2014
Lundbeck Foundation
2014
Bispebjerg Hospital
2014
Copenhagen University Hospital
2014
Broad Institute
2014
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— Recent evidence points to functional Ca 2+ -dependent K + (SK) channels in the heart that may govern atrial fibrillation (AF) risk, but underlying mechanisms are unclear. This study addressed role of SK repolarization and AF persistence a canine model. Methods Results— Electrophysiological variables were assessed dogs subjected remodeling by 7-day tachypacing (AT-P), as well controls. Ionic currents single-channel properties measured isolated cardiomyocytes patch clamp. NS8593,...
Significance Spider venom is a rich source of peptides, many targeting ion channels. We assessed peptide, Hm1a, as potential targeted therapy for Dravet syndrome, the genetic epilepsy linked to mutation in gene encoding sodium channel alpha subunit Na V 1.1. Cell-based assays showed Hm1a was selective hNa 1.1 over other and potassium Utilizing mouse model restored inhibitory neuron function significantly reduced seizures mortality heterozygote mice. Evidence from structure modeling suggest...
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...
The cardiac action potential is generated by a concerted of different ion channels and transporters. Dysfunction any these membrane proteins can give rise to arrhythmias, which particularly true for the repolarizing potassium channels. We suggest that an increased repolarization current could be new antiarrhythmic principle, because it possibly would attenuate afterdepolarizations, ischemic leak currents, re-entry phenomena. Repolarization myocytes crucially dependent on late rapid delayed...
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...
Large-conductance Ca<sup>2+</sup>- and voltage-activated K<sup>+</sup> channels (Kca1.1/BK/MaxiK) are widely expressed ion channels. They provide a Ca<sup>2+</sup>-dependent feedback mechanism for the regulation of various body functions such as blood flow, neurotransmitter release, uresis, immunity. In addition, mitochondrial channel with KCa1.1-resembling properties has been found in heart, where it may be involved energy consumption. present study, effect novel NeuroSearch compound,...
Transient outward potassium current (I(to)) is thought to be central the pathogenesis of Brugada syndrome (BrS). However, an I((to)) activator has not been available with which validate this hypothesis. Here, we provide a direct test hypothesis using novel I(to) activator, NS5806.Isolated canine ventricular myocytes and coronary-perfused wedge preparations were used. Whole-cell patch-clamp studies showed that NS5806 (10 microM) increased peak at +40 mV by 79 +/- 4% (24.5 2.2 43.6 3.4 pA/pF,...
BACKGROUND AND PURPOSE Positive allosteric modulation of α4β2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH Effects were evaluated in vitro using fluorescence‐based Ca 2+ imaging electrophysiological voltage clamp experiments Xenopus oocytes, mammalian cells thalamocortical neurons. In vivo compound models covering range...
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...
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...