Vladimir Matchkov

Vladimir Matchkov
  • Ph.d, DMSc
  • Professor (Associate) at Aarhus University

About

167
Publications
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3,524
Citations
Current institution
Aarhus University
Current position
  • Professor (Associate)

Publications

Publications (167)
Article
Aim In animal models and human cerebral arteries, the changes in endothelial cell (EC)‐large conductance calcium‐activated potassium channel (BK Ca ) distribution, expression, and function were determined in hypoxia and ischemic stroke. The hypothesis that hypoxia and ischemic stroke induce EC‐BK Ca in cerebral arteries was examined. Methods Immun...
Article
BACKGROUND More than half of patients with ischemic stroke experience futile reperfusion, increasing the risk of death and disabilities despite a successful recanalization. The reason behind this is debated, and we aim to investigate cerebrovascular changes toward a broader understanding of these conditions. We hypothesize that ischemic stroke repe...
Article
Background Familial hemiplegic migraine (FHM) types 1–3 are associated with protein-altering genetic variants in CACNA1A, ATP1A2 and SCN1A, respectively. These genes have also been linked to epilepsy. Previous studies primarily focused on phenotypes, examining genetic variants in individuals with characteristic FHM symptoms. This study aimed to inv...
Preprint
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Microvascular pulsatility in the brain is crucial for sustaining the delicate balance between the brain's metabolic demands and blood supply, as it affects nutrient exchange, waste removal and blood-brain barrier permeability. Abnormal pulsatility, associated with ageing or vascular risk factors, may impair the clearance of metabolic waste or contr...
Article
Familial hemiplegic migraine type 2 (FHM2) is linked to Na,K-ATPase α 2 isoform mutations, including that of G301R. Mice heterozygous for this mutation ([Formula: see text]) show cerebrovascular hypercontractility associated with amplified Src kinase signaling, and exaggerated neurovascular coupling. This study hypothesized that targeting Na,K-ATPa...
Preprint
Membrane depolarization is implicated in the activation of the NLRP3 inflammasome. Downregulation of endothelial Ca2+-activated K+ channels type 2.3 (K Ca 2.3) and endothelin-1 (ET-1) upregulation in the corpus cavernosum (CC) are associated with erectile dysfunction. We hypothesized that opening K Ca 2.2/2.3 channels could reverse erectile dysfunc...
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Large‐conductance, calcium‐activated potassium channels (BK channels) and the Na/K‐ATPase are expressed universally in vascular smooth muscle. The Na/K‐ATPase may act via changes in the intracellular Ca²⁺ concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels. Whether BK channels func...
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In the vascular wall, the Na,K-ATPase plays an important role in the control of arterial tone. Through cSrc signaling, it contributes to the modulation of Ca2+ sensitivity in vascular smooth muscle cells. This review focuses on the potential implication of Na,K-ATPase-dependent intracellular signaling pathways in severe vascular disorders; ischemic...
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The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output and myocardial perfusion without affecting blood pressure in humans, but the cardiovascular sites of action remain obscure. Here, we test the hypothesis in rats that 3-OHB acts directly on the heart to increase cardiac contractility and directly on blood vessels to lower systemic va...
Article
Fatal poisonings where both methadone and quetiapine are detected post‐mortem occurs frequently in legal autopsy cases. It is unclear whether quetiapine increases the risk of fatal methadone poisoning or if it is merely detected due to widespread use. We hypothesized that methadone and quetiapine would have additive toxic effects on respiratory rat...
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The genetic architecture of the QT interval, defined as the period from onset of depolarisation to completion of repolarisation of the ventricular myocardium, is incompletely understood. Only a minor part of the QT interval variation in the general population has been linked to autosomal variant loci. Altered X chromosome dosage in humans, as seen...
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Background Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalizati...
Article
Background: Despite vessel recanalization, up to 67% of ischemic-stroke patients experience futile reperfusion increasing the risk of neurological morbidity and death. Arterial hypercontractility has been suggested to underlie the no-flow phenomenon, however, this remains to be fully elucidated. Parenchymal arteries in the area surrounding the isch...
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Two α-isoforms of the Na+,K+-ATPase (α1 and α2) are expressed in the cardiovascular system, and it is unclear which isoform is the preferential regulator of contractility. Mice heterozygous for the familial hemiplegic migraine type 2 (FHM2) associated mutation in the α2-isoform (G301R; α2+/G301R mice) have decreased expression of cardiac α2-isoform...
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Laser speckle contrast imaging is a technique that provides valuable physiological information about vascular topology and blood flow dynamics. When using contrast analysis, it is possible to obtain detailed spatial information at the cost of sacrificing temporal resolution and vice versa. Such a trade-off becomes problematic when assessing blood d...
Preprint
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A bstract SorCS2 is involved in trafficking of membrane receptors and transporters. SorCS2 is implicated in brain disorders, but the mechanism remains uncertain. We hypothesized that SorCS2 expression is important for neurovascular coupling. Brains from P8 and 2-month-old wild type mice were stained for SorCS2 and compared to SorCS2 knockouts ( Sor...
Article
Background: A variant in the SLC4A3 anion exchanger has been identified as a novel cause of short QT syndrome (SQTS), but the clinical importance of SLC4A3 as a cause of SQTS or sudden cardiac death (SCD) remains unknown. Objective: To investigate the prevalence of potential disease-causing variants using gene panels including SLC4A3. Methods:...
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Dietary potassium (K+) supplementation is associated with a blood pressure (BP) lowering effect, but not all studies agree. Here we examined the effects of short and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP...
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Heterozygous mice (α2+/G301R mice) for the migraine-associated mutation (G301R) in the Na+,K+-ATPase α2-isoform have decreased expression of cardiovascular α2-isoform. The α2+/G301R mice exhibit a pro-contractile vascular phenotype associated with decreased left ventricular ejection fraction. However, the integrated functional cardiovascular conseq...
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Background: Several local Ca²⁺ events are characterized in smooth muscle cells. We have previously shown that an inhibitor of the Na,K-ATPase, ouabain induces spatially restricted intracellular Ca²⁺ transients near the plasma membrane, and suggested the importance of this signaling for regulation of intercellular coupling and smooth muscle cell con...
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The damaging effect of ionizing radiation (IR) on skeletal muscle Na,K-ATPase is an open field of research. Considering a therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against the IR-induced disturbances of Na,K-ATPase function in rat diaphragm muscle that co-expresses the α1 and α2 isozyme...
Preprint
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Background. Despite recanalization after ischemic stroke, neurovascular coupling, i.e., the local hyperaemic response to neuronal activity, is impaired in peri-ischemic brain regions. Such reduction in neurovascular coupling may contribute to neurological deterioration over time. The mechanism underlying dysfunctional neurovascular coupling followi...
Article
Background: Impaired mineral ion metabolism is a hallmark of CKD-metabolic bone disorder. It can lead to pathologic vascular calcification and is associated with an increased risk of cardiovascular mortality. Loss of calcium-sensing receptor (CaSR) expression in vascular smooth muscle cells exacerbates vascular calcification in vitro. Conversely,...
Article
The choroid plexus epithelium (CPE) has recently gained increasing interest as a potential target tissue to manipulating cerebrospinal fluid (CSF) production (1). It is therefore crucial to identify the basolateral Na ⁺ transport mechanisms that are involved in CSF secretion, as it would be accessible from the blood side and thereby hold promise fo...
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Background Mutations in ATP1A2 gene encoding the Na,K‐ATPase α 2 isoform are associated with familial hemiplegic migraine type 2. Migraine with aura is a known risk factor for heart disease. The Na,K‐ATPase is important for cardiac function, but its role for heart disease remains unknown. We hypothesized that ATP1A2 is a susceptibility gene for hea...
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Objective Investigating the cardiovascular system is challenging due to its complex regulation by humoral and neuronal factors. Despite this complexity, many existing research methods are limited to the assessment of a few parameters leading to an incomplete characterization of cardiovascular function. Thus, we aim to establish a murine in vivo mod...
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Neurovascular coupling ensures rapid and precise delivery of O2 and nutrients to active brain regions. Chronic stress is known to disturb neurovascular signaling with grave effects on brain integrity. We hypothesized that stress-induced neurovascular disturbances depend on stress susceptibility. Wistar male rats were exposed to 8 weeks of chronic m...
Article
In the last years, the field of inheritable ventricular arrhythmia disease modelling has changed significantly with a push towards the use of novel cellular cardiomyocyte based models. However, there is a growing need for new in vivo models to study the disease pathology at the tissue and organ level. Zebrafish provide an excellent opportunity for...
Article
To provide the first description of the exact location of primary pacemaker of the squamate heart, we used sharp microelectrode impalements and optical mapping of isolated sinus venosus preparations from Burmese pythons. We located the dominant pacemaker site at the base of the right leaflet of the sinoatrial valve (SAV), but latent pacemakers were...
Article
The study by Kurtz et al.1 validated the hypothesis that the Na/K‐ATPase controls metabolic capacity via Src kinase signalling. They found that regulatory attenuation of Src kinase signalling by the Na/K‐ATPase α1 isoform correlates with improved metabolic reserve and substrate flexibility that increase exercise endurance. This comes at the cost of...
Article
Despite successful recanalization, a significant number of patients with ischemic stroke experience impaired local brain tissue reperfusion with adverse clinical outcome. The cause and mechanism of this multifactorial complication are yet to be understood. At the current moment, major attention is given to dysfunction in blood-brain barrier and cap...
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The thiazide-sensitive sodium-chloride-cotransporter (NCC) in the kidney distal convoluted tubule (DCT) plays an essential role in sodium and potassium homeostasis. Here, we demonstrate that NCC activity is increased by the β2-adrenoceptor agonist salbutamol, a drug prevalently used to treat asthma. Relative to β1-adrenergic receptors, the β2-adren...
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Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is characteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis...
Article
Background The electroneutral Na⁺/HCO3⁻ cotransporter NBCn1 (Slc4a7) is expressed in basolateral membranes of renal medullary thick ascending limbs (mTALs). However, direct evidence that NBCn1 contributes to acid-base handling in mTALs, urinary net acid excretion, and systemic acid-base homeostasis has been lacking. Methods Metabolic acidosis was...
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Introduction The average age of the diving population is rising, and the risk of atherosclerosis and cardiovascular disease in divers are accordingly increasing. It is an open question whether this risk is altered by diving per se. In this study, we examined the effect of 7-weeks simulated diving on endothelial function and mitochondrial respiratio...
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Transglutaminase 2 (TG2) is an enzyme which in the open conformation exerts transamidase activity, leading to protein cross-linking and fibrosis. In the closed conformation, TG2 participates in transmembrane signaling as a G protein. The unspecific transglutaminase inhibitor cystamine causes vasorelaxation in rat resistance arteries. However, the r...
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A Ca2+ -activated Cl- channel protein, ANO1, is expressed in vascular smooth muscle cells where Cl- current is thought to potentiate contraction by contributing to membrane depolarization. However, there is an inconsistency between previous knockout and knockdown studies on ANO1's role in small arteries. In this study, we assessed cardiovascular fu...
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Membrane transporters and their functional contribution in vasculature change during early postnatal development. Here we tested the hypothesis that the contribution of Cl− channels to arterial contraction declines during early postnatal development and this decline is associated with the trophic sympathetic influence. Endothelium‐denuded saphenous...
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Acid-base conditions modify artery tone and tissue perfusion but the involved vascular sensing mechanisms and disease consequences remain unclear. We experimentally investigated transgenic mice and performed genetic studies in a UK-based human cohort. We show that endothelial cells express the putative HCO3--sensor receptor-type tyrosine-protein ph...
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Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclero...
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The ability of exogenous low ouabain concentrations to affect claudin expression and therefore epithelial barrier properties was demonstrated previously in cultured cell studies. We hypothesized that chronic elevation of circulating ouabain in vivo can affect the expression of claudins and tight junction permeability in different tissues. We tested...
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While the role of circulating ouabain-like compounds in the cardiovascular and central nervous systems, kidney and other tissues in health and disease is well documented, little is known about its effects in skeletal muscle. In this study, rats were intraperitoneally injected with ouabain (0.1–10 µg/kg for 4 days) alone or with subsequent injection...
Article
Na,K-ATPase is a membrane transporter critically important for skeletal muscle function. Mdx and Bla/J mice are the experimental models of Duchenne muscular dystrophy and dysferlinopathy. The molecular mechanism behind myodystrophy is of therapeutic importance; however, the detailed role of Na,K-ATPase in these dysfunctions has not previously been...
Article
In general, a high NaCl intake is associated with increased blood pressure (BP), whereas dietary potassium intake has a negative correlation with BP, cardiovascular (CV) outcomes and reduces the ‘salt sensitivity’ of BP. High K ⁺ intake reduces activity of the sodium‐chloride cotransporter NCC, promoting natiuresis, which is a proposed major mechan...
Article
Introduction The aim of this study was to build an implant and benchmark it for further improvement, specifically aimed to measure periphery nerves in rats. The nerve algorithm was based on the Qtrac approach for measurements of excitability measurements on motor and sensory nerves. This design was designed for enhanced measurements of nerve functi...
Article
Aim: Cardiovascular complications, including cardiac arrhythmias, result in high morbidity and mortality in patients with type-2 diabetes mellitus (T2DM). Clinical and experimental data suggest electrophysiological impairment of the natural pacemaker of the diabetic heart. The present study examined sinoatrial node (SAN) arrhythmias in a mouse mod...
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A detailed description of the electrophysiological features of cardiomyocytes in the various contractile chambers of the vertebrate heart is essential to understand the evolution of cardiac electrical activity, yet very little is known about reptiles. The present study characterizes major ionic currents (INa, ICaL, IKr, IK1 and IKACh) and action po...
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Aims: Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na,K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R) were shown to have elevated cerebrovascular tone and, thus, hypoperfusion that migh...
Article
Recently, we found cardioprotective effects of ischemic preconditioning (IPC), and from a blocker of KCNQ voltage-gated K+ channels (KV7), XE991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone), in isolated rat hearts. The purpose of the present study was to investigate the cardiovascular effects of IPC and XE991 and whether they are cardioprotec...
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Introduction The number of divers is rising every year, including an increasing number of aging persons with impaired endothelial function and concomitant atherosclerosis. While diving is an independent modulator of endothelial function, little is known about how diving affects already impaired endothelium. In this study, we questioned whether divi...
Article
Background: Perivascular adipose tissue (PVAT) reduces vascular tone in isolated arteries in vitro, however there are no studies of PVAT effects on vascular tone in vivo. In vitro adipocyte β3-adrenoceptors play a role in PVAT function via secretion of the vasodilator adiponectin. Objective: We have investigated the effects of PVAT on vessel dia...
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Cardiovascular diseases are the first cause of death globally. Their early diagnosis requires ultrasensitive tools enabling the detection of minor structural and functional alterations in small arteries. Such analyses have been traditionally performed with video imaging-based myographs, which helped to investigate the pathophysiology of the microve...
Article
Background Diabetic neuropathy (DN) is a common condition. At the moment, it is unclear how and when the autonomic changes develop in relation to the somatosensory signs. As alternative, animal-studies using experimental models of diabetic neuropathy represent a way to elucidate the sensory and autonomic changes associated with development of DN. T...
Article
Familial hemiplegic migraine type 2 (FHM2) is migraine with aura that is associated with mutations in the Na, K‐ATPase α2 isoform including G301R mutation. These FHM2‐associated mutations result in reduced expression of the α2 Na, K‐ATPase. Migraine attack in FHM2 patients is characterized by sequential hypo‐ and hyperperfusion of the affected hemi...
Article
Diabetes is associated with altered contractile responses of small arteries. In the streptozotocin (STZ) induced rat model of diabetes enhanced contractility several groups have reported an increased contractility. In this study we tested the hypothesis that chloride is important for the enhanced contractility in the STZ rats. Diabetes was induced...
Article
Dysferlin protein plays a key role in the multimolecular complex responsible for the maintenance of sarcolemma integrity and skeletal muscle cell functioning. We studied the membrane distribution of nicotinic acetylcholine receptors and α2 isoform of Na,K-ATPase in motor endplates of m. soleus in dysferlin-deficient Bla/J mice (a dysferlinopathy mo...
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Key points The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilatation caused by CGRP (and possibly substance P) released from sensory‐motor nerves and vasoconstriction caused by noradrenaline, ATP and neuropeptode Y release from sympathetic nerves. Most studies on perivascular nerve‐mediated vasodilatation ar...
Article
New findings: What is the topic of this review? This review considers the role of the Na,K-ATPase in cerebrovascular function and how it might be changed in familial hemiplegic migraine type 2 (FHM2). The primary focus will be involvement of the Na,K-ATPase isoforms in regulation of cerebrovascular tone. What advances does it highlight? The review...
Article
New findings: What is the topic of this review? This symposium report discusses the previously unrecognized pro-contractile role of chloride ions in rat arteries at early stages of postnatal development. What advances does it highlight? It highlights the postnatal decline in the contribution of chloride ions to regulation of arterial contractile r...
Chapter
The Na,K-ATPase is an enzyme essential for ion homeostasis in all cells. Over the last decades, it has been well-established that in addition to the transport of Na ⁺ /K ⁺ over the cell membrane, the Na,K-ATPase acts as a receptor transducing humoral signals intracellularly. It has been suggested that ouabain-like compounds serve as endogenous modu...
Article
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Inhibition of the Na,K-ATPase by ouabain potentiates vascular tone and agonist-induced contraction. These effects of ouabain varies between different reports. In this study, we assessed whether the pro-contractile effect of ouabain changes with arterial diameter and the molecular mechanism behind it. Rat mesenteric small arteries of different diame...
Article
The compressed gas breath during diving augments partial pressure of oxygen causing the oxygen concentration of the blood to increase above normal (hyperoxia). Hyperoxia in combination with gas bubbles that develop during the decompression (ascent) phase, likely causing oxidative stress, including transient endothelial dysfunction in venous and art...
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Familial hemiplegic migraine type 2 (FHM2) is associated with inherited point-mutations in the Na,K-ATPase α2 isoform, including G301R mutation. We hypothesized that this mutation affects specific aspects of vascular function, and thus compared cerebral and systemic arteries from heterozygote mice bearing the G301R mutation (Atp1a2+/−G301R) with wi...
Article
Aims: The Na,K-ATPase is involved in a large number of regulatory activities including cSrc-dependent signalling. Upon inhibition of the Na,K-ATPase with ouabain, cSrc activation is shown to occur in many cell types. This study tests the hypothesis that acute potentiation of agonist-induced contraction by ouabain is mediated through Na,K-ATPase-cS...
Article
TMEM16A is essential for Ca2+ -activated Cl- channel conductance in vascular smooth muscle. The importance of TMEM16A for agonist-induced vascular constriction and blood pressure control is, however, under debate. Previous studies suggested that TMEM16A might have a complex cellular function beyond being essential for the Ca2+ -activated Cl- conduc...
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Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduce...
Article
Key points: Substantial information on rat mesenteric small artery physiology and pharmacology based on in vitro experiments is available. Little is known about the relevance of this for artery function in vivo. We here present an intravital model where rat mesenteric small artery diameters are studied under isolated and controlled conditions in s...
Article
Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events which might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6 - 12 h) hindlimb suspensi...
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The cerebrospinal fluid (CSF) pH influences brain interstitial pH and, therefore, brain function. We hypothesized that the choroid plexus epithelium (CPE) expresses the vacuolar H⁺‐ATPase (V‐ATPase) as an acid extrusion mechanism in the luminal membrane to counteract detrimental elevations in CSF pH. The expression of mRNA corresponding to several...
Article
Cl⁻ and HCO3⁻ are the most prevalent membrane-permeable anions in the intra- and extracellular spaces of the vascular wall. Outwardly directed electrochemical gradients for Cl⁻ and HCO3⁻ permit anion channel opening to depolarize vascular smooth muscle and endothelial cells. Transporters and channels for Cl⁻ and HCO3⁻ also modify vascular contracti...
Article
Full-text available
Na,K-ATPase is a protein ubiquitously expressed in the plasma membrane of all animal cells and vitally essential for their functions. A specialized functional diversity of the Na,K-ATPase isozymes is provided by molecular heterogeneity, distinct subcellular localizations, and functional interactions with molecular environment. Studies over the last...
Article
The role of ATP for vascular function is well documented. In this study we wanted to assess the role of purinergic signaling for rat small mesenteric arteries in vivo. Rats were anesthetized with Ketamin/Xylazin and the intestine exteriorized through a laparotomy. A small mesenteric artery segment was positioned in a 200 μl reservoir and the diamet...
Article
Oxidative stress is associated with the pathogenesis of hypertension. Decreased bioavailability of nitric oxide (NO) is one of the mechanisms involved in the pathogenesis. It has been suggested that physical exercise could be a potential non-pharmacological strategy in treatment of hypertension because of its beneficial effects on oxidative stress...
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The Na,K-ATPase is essential for the contractile function of skeletal muscle, which expresses the α1 and α2 subunit isoforms of Na,K-ATPase. The α2 isozyme is predominant in adult skeletal muscles and makes a greater contribution in working compared with noncontracting muscles. Hindlimb suspension (HS) is a widely used model of muscle disuse that l...
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Background and Purpose Vasodilatation may contribute to the neuroprotective and vascular anti‐remodelling effect of the tissue transglutaminase 2 (TG2) inhibitor cystamine. Here, we hypothesized that inhibition of TG2 followed by blockade of smooth muscle calcium entry and/or inhibition of Rho kinase underlies cystamine vasodilatation. Experimenta...
Article
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The extracellular calcium-sensing receptor, CaSR, is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vas...
Article
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The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca2+-activated K+ channels (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa depends on Ca2+out. Also it has been suggested that K+ is important through loc...
Article
Major depression is known to be associated with cardiovascular abnormalities and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress, and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with >30% reduction in sucrose intake af...
Article
Background and purpose: T16A(inh)-A01, CaCC(inh)-A01 and MONNA are identified as selective inhibitors of the TMEM16A calcium-activated chloride channel (CaCC). The aim of this study was to examine the chloride-specificity of these compounds on isolated resistance arteries in the presence and absence (±) of extracellular chloride. Experimental app...
Article
Antidepressants affecting norepinephrine (NE) reuptake are known to increase the risk for hypertension. Anhedonia ‐ a decreased ability to experience pleasures ‐ is a central symptom in depression and can be evoked in preclinical models exploring the role of the stressful environment in mediating affective signs and autonomic function. Some rats ex...
Article
Ca(2+)-activated Cl(-) channels (CaCCs) have numerous functions in the body and are potential players in the control of blood pressure. The CaCCs represent a heterologous group including at least two protein families; TMEM16 and bestrophins. CaCCs expression has been shown in the kidney, the heart and blood vessels. Agonist-stimulated Ca(2+)-activa...
Article
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This study examines the isoform-specific effects of short-term hindlimb suspension (HS) on the Na,K-ATPase in rat soleus muscle. Rats were exposed to 24-72 h of HS and we analyzed the consequences on soleus muscle mass and contractile parameters; excitability and the resting membrane potential (RMP) of muscle fibers; the electrogenic activity, prot...
Article
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Major depression and cardiovascular diseases are two of the most prevalent health problems in western society and an association between them is generally accepted. Although the specific mechanism behind this comorbidity remains to be elucidated, it is clear that it has a complex multifactorial character including a number of neuronal, humoral, imm...
Article
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The presence of Ca(2+)-activated Cl(–) currents (I(Cl(Ca))) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca(2+)]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with I(Cl(Ca)). Two distinc...
Article
Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the chronic mild stress model, some rats develop depression-like symptoms (including "anhedonia"), whereas others are stress resilient. After 8 weeks of chr...
Article
We have previously demonstrated two Ca ²⁺ activated Cl ‐ conductances in smooth muscle cells (SMC). One which is cGMP dependent and Zn ²⁺ sensitive (IClcGMP) and one which is not (ICl). We have also shown that IClcGMP, but not ICl, disappears after knock‐down of bestrophin3. We here tested the role of TMEM16A for the two currents. In vivo downregul...

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