A5082541348- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Cardiac Arrhythmias and Treatments
- Pancreatic function and diabetes
- Ion Transport and Channel Regulation
- Liver physiology and pathology
- Diet, Metabolism, and Disease
- Adenosine and Purinergic Signaling
- Neuroscience and Neural Engineering
- Cardiovascular Effects of Exercise
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Plant Genetic and Mutation Studies
- Metabolism, Diabetes, and Cancer
- Fibroblast Growth Factor Research
- Genomics, phytochemicals, and oxidative stress
- Cardiomyopathy and Myosin Studies
- Atrial Fibrillation Management and Outcomes
- Cannabis and Cannabinoid Research
- Biomedical Research and Pathophysiology
- Liver Disease Diagnosis and Treatment
- Plant Reproductive Biology
- Neuroscience and Neuropharmacology Research
- Mass Spectrometry Techniques and Applications
University of Copenhagen
2007-2018
Danish National Research Foundation
2011-2018
National Research Foundation
2011-2013
Analysis of phosphorylated proteins from the hearts mice given drugs targeting β-adrenergic receptors may aid in treating heart disease.
AimsGenetic factors may be important in the development of atrial fibrillation (AF) young. KCNA5 encodes potassium channel α-subunit KV1.5, which underlies voltage-gated atrial-specific current IKur. KCNAB2 KVβ2, a β-subunit increases Three studies have identified loss-of-function mutations patients with idiopathic AF. We hypothesized that early-onset lone AF is associated high prevalence genetic variants and KCNAB2.
Ion transport processes are highly energy consuming. It is therefore critical to couple ion the metabolic state of cell. An important player in this coupling appears be AMP-activated protein kinase (AMPK). This becomes activated during conditions cellular stress and well-known for its role promoting ATP-generating catabolic pathways while turning off ATP-utilizing anabolic pathways. Over past decade AMPK has also emerged as a key regulator channel activity an increasing number channels...
The potassium channel Kv7.1 is expressed in the heart, where it contributes to repolarization of cardiac action potential. Additionally, epithelial tissues playing a role salt and water transport. We recently demonstrated that surface-expressed internalized response polarization Madin-Darby canine kidney (MDCK) cell line this was mediated by activation protein kinase C (PKC). In study, pathway downstream PKC, which leads internalization upon polarization, elucidated. show confocal microscopy...
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...
Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs essential for repolarization. Gain-of-function mutation in KCNQ1, gene encoding pore-forming α-subunit of channel (KV 7.1), was first ion dysfunction to be associated with familial AF. We hypothesized that early-onset lone AF a high prevalence mutations KCNQ1.We bidirectionally sequenced entire coding sequence KCNQ1 209 unrelated patients (<40 years) and investigated identified functionally...
Brugada syndrome (BrS) is a rare inherited disease that can give rise to ventricular arrhythmia and ultimately sudden cardiac death. Numerous loss-of-function mutations in the sodium channel Nav1.5 have been associated with BrS. However, few auxiliary Navβ1-4 subunits linked this disease. Here we investigated differences expression function between Navβ1 Navβ1b whether H162P/Navβ1b mutation found BrS patient likely be underlying cause of The impact Navβ was by patch-clamp electrophysiology,...
Extracellular ATP is an important short-range signaling molecule that promotes various physiological responses virtually in all cell types, including pancreatic β-cells. It well documented β-cells release through exocytosis of insulin granules upon glucose stimulation. We hypothesized might stimulate other non-vesicular mechanisms. Several purinergic receptors are found and there increasing evidence regulates β-cell functions survival. One the may be relevant P2X7 receptor, but its detailed...
It has recently been shown that hepatocyte growth factor activator inhibitor-2 (HAI-2) is able to suppress carcinogenesis induced by overexpression of matriptase, as well cause regression individual established tumors in a mouse model system. However, the role HAI-2 poorly understood. In this study, we describe 3 mutations binding loop Kunitz domain 1 (K42N, C47F and R48L) delay SEA cleavage leading accumulation non-SEA cleaved matriptase endoplasmic reticulum (ER). We suggest that, like...
The potassium channel K V 7.1 is expressed in the heart where it contributes to repolarization of cardiac action potential. In addition, epithelial tissues plays a role salt and water transport. Mutations kcnq1 gene can lead long QT syndrome deafness, several mutations have been described as trafficking mutations. To learn more about basic mechanisms that regulate surface expression, we investigated during polarization process cell line Madin-Darby Canine Kidney (MDCK) using modified version...
The voltage-gated potassium channel KV 7.1 is regulated by non-pore forming regulatory KCNE β-subunits. Together with KCNE1, it forms the slowly activating delayed rectifier current IKs . However, where subunits assemble and which of determines localization -complex has not been unequivocally resolved yet. We employed trafficking-deficient KCNE1 mutants to investigate trafficking using polarized Madin-Darby Canine Kidney cell line. find that assembly happens early in secretory pathway but...
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...
The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, the accessory subunit KCNE1 forms slowly activating delayed-rectifier current current, which is enhanced by protein kinase A (PKA)-mediated phosphorylation. observed increase requires phosphorylation of presence KCNE1. However, PKA also stimulates currents tissues, such as colon, where does not coassemble with Here, we demonstrate that activity significantly impacts subcellular...
Purpose: Genetic factors contribute significantly to the pathogenesis of atrial fibrillation (AF) but molecular defects in majority patients with AF are unknown. The two-pore domain potassium channel, K2P3.1 (TASK-1) has atrial-specific expression and been recently shown be a major determinant resting membrane potential human cardiomyocytes. We hypothesized that mutations KCNK3 gene encodes TASK-1 might predispose AF.
The voltage-gated potassium channel KV11.1 has been originally cloned from the brain and is expressed in a variety of tissues. role phosphorylation for function matter debate. In this study, we aimed to elucidate extent protein kinase D mediated phosphorylation.We employed mass spectrometry, whole-cell patch clamp electrophysiology, confocal microscopy, site-directed mutagenesis, western blotting.Using tissue rat mouse, mapped several phosphorylated residues by LC-MS spectrometry identified...