Soren Grubb

Soren Grubb
University of Copenhagen · Faculty of Health and Medical Sciences

PhD

About

31
Publications
2,856
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504
Citations
Additional affiliations
February 2019 - present
University of Copenhagen
Position
  • Professor (Assistant)
February 2017 - February 2019
University of Copenhagen
Position
  • PostDoc Position
September 2014 - September 2016
University of Copenhagen
Position
  • PostDoc Position

Publications

Publications (31)
Preprint
The microvascular inflow tract (MIT), comprising the penetrating arterioles, precapillary sphincters, and first order capillaries, is the bottleneck for brain blood flow and energy supply. However, the exact structural and functional alterations of the MIT during aging remain elusive. In vivo 4-dimensional two-photon imaging showed an age-dependent...
Article
The neurovascular coupling ensures that cerebral activity is matched by the relevant blood flow. The control of the blood flow is mediated by capillaries and by the precapillary aterioles. It is the tone of the mural cells, which include pericytes, smooth muscle cells and cells with intermediate phenotypes between pericytes and smooth muscle cells,...
Article
Full-text available
Active nerve cells release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling and the basis of BOLD functional neuroimaging signals. Here, we reveal a mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and firs...
Article
Active nerve cells produce and release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling, which is the basis of the BOLD (blood-oxygen-level-dependent) functional neuroimaging signals. We here reveal a unique mechanism for cerebral blood flow control, a precapillary sphincter a...
Article
Cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) are used to study cardiogenesis and mechanisms of heart disease, and are being used in methods for toxiological screening of drugs. The phenotype of stem-cell-derived CMs should ideally resemble native CMs. Here, we compare embryonic/fetal...
Article
Aims: Abnormal intracellular Ca 2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca 2+ waves in left atria from normal and failing dog hearts. Methods and results: Intracellular Ca 2+ cycling was studied using confocal microscopy during rapi...
Article
Full-text available
The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESC) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of CMs derived from hESCs (hESC-CMs) and examined how the expression of CM subtypes correspond to...
Article
Aim: In this study, we investigate the impact of altered action potential durations (APD) on ventricular repolarization time and proarrhythmia in mice with and without genetic deletion of the K+-channel interacting protein 2 (KChIP2(-/-) and WT, respectively). Moreover, we examine the interrelationship between the dispersion of repolarization time...
Article
Full-text available
Purpose of the study: Downregulation of ventricular K+ channel-interacting protein 2 (KChIP2) and loss of the transient outward K+ current (Ito), is observed in failing hearts. In this study, we investigate the impact of KChIP2 and heart failure (HF) on action potential duration (APD) and repolarization time (RT) in mouse hearts. We hypothese that...
Article
We previously documented triggered calcium (Ca) wave (TCW) development in atrial myocytes from large animals during rapid pacing. The goal of this study was to investigate the relationship between Ca transient (CaT) alternans and TCWs in atrial myocytes from normal and failing hearts. Ca cycling was measured via confocal microscopy in atrial myocyt...
Article
Full-text available
The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tac...
Article
Inherited ion channelopathies and electrical remodelling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast recovering transient...
Article
Full-text available
The heart rate in horses can vary between 30 and 250 beats per minute. This suggests an important role for a dynamic regulation of the repolarizing potassium currents.Methods and Results: Kv7.1 and KCNE1 that underlie the slow delayed rectifying current (IKs) as well as Kv11.1 and KCNE2 that underlie the rapid delayed rectifying current (IKr) were...
Article
KV 4 together with KV Channel-Interacting Protein 2 (KChIP2) mediate the fast recovering transient outward potassium current (Ito,f ) in the heart. KChIP2 is downregulated in human heart failure (HF), potentially underlying the loss of Ito,f . We investigated remodeling associated with HF hypothesizing that KChIP2 plays a central role in the modula...
Article
Combined prolongation and spatial heterogeneity of cardiac action potential (AP) duration is proarrhythmic in larger mammals; however the short murine AP suggests a different mechanism underlying arrhythmia induction. Expression of KChIP2 is critical for the stabilization of Kv4.2 in mice, and KChIP2-/- abolishes the transient outward K+ current, I...
Article
Full-text available
Anoctamin 6 (ANO6), also known as TMEM16F, has been shown to be a calcium-activated anion channel with delayed calcium activation. The cellular function of ANO6 is under debate, and different groups have come to different conclusions about ANO6's physiological role. Although it is now quite well established that ANO6 is distinct from the volume-reg...
Article
Abnormal ventricular repolarization in ion channelopathies and heart disease is a major cause of ventricular arrhythmias and sudden cardiac death. K+ channel-interacting protein 2 (KChIP2) expression is significantly reduced in human heart failure (HF), contributing to a loss of the transient outward K+ current (I-to). We aim to investigate the pos...
Chapter
Microscopic analyses of calcium (Ca2+) cycling in enzymatically isolated skeletal and cardiac myocytes using Ca2+-sensitive fluorophores is a widely used method of visualizing, characterizing, and quantifying the basis of both normal and pathological excitation?contraction (E-C) coupling. Improvements in Ca2+ fluorophores and the advent of confocal...
Article
Full-text available
Members of the TMEM16 (Anoctamin) family of membrane proteins have been shown to be essential constituents of the Ca(2+)-activated Cl(-) channel (CaCC) in many cell types. In this study, we have investigated the electrophysiological properties of mouse TMEM16F. Heterologous expression of TMEM16F in HEK293 cells resulted in plasma membrane localizat...
Article
Full-text available
AimsAtrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada Syndrome. Here we aim to determi...
Article
Triggered Ca2+ waves develop during rapid pacing in atrial myocytes and are therefore likely to contribute to action potential (AP) duration, thus establishing repolarization gradients and causing reentry. The goal of this study was to investigate how Ca2+ wave properties are altered in heart failure (HF). Myocytes were isolated from the left atriu...
Article
Cardiac myocytes exhibit a fast recovering transient outward potassium current (Ito,f) that is conducted by the channel proteins Kv4 + KChIP2. Heart failure (HF) is associated with a reduction of outward K+-currents and a downregulation of KChIP2. In this study, we investigated the electrophysiological role of KChIP2 in mice with HF.HF induced by t...
Article
Abnormal ventricular repolarization in ion channelopathies and heart disease are major causes of ventricular arrhythmias and sudden cardiac death. The level of K+ channel-interacting protein 2 (KChIP2) is significantly reduced in human heart failure (HF), contributing to a loss of transient outward K+ current (Ito). We have previously shown that th...
Article
Full-text available
Electrophysiological remodeling of cardiac potassium ion channels is important in the progression of heart failure. A reduction of the transient outward potassium current (I(to)) in mammalian heart failure is consistent with a reduced expression of potassium channel interacting protein 2 (KChIP2, a K(V)4 subunit). Approaches have been made to inves...
Article
INTRODUCTION: The Brugada syndrome (BrS) is characterized by an atypical right bundle block pattern with ST segment elevation and T wave inversion in the right precordial leads. The disease transmission is autosomal dominant with incomplete penetrance. We found 3 novel mutations in SCN5A in two independent families diagnosed with BrS.METHODS: We pe...
Article
Full-text available
Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias. The objective of this study is to characterize a novel mutation in Na(v)1.5 found in a newborn with fetal chaotic atrial tachycardia, post-partum intraventri...

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