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Influence of Kv11.1 (hERG1) K + channel expression on DNA damage induced by the genotoxic agent methyl methanesulfonate Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-15 Sara Fernández-Villabrille, Enol Álvarez-González, Francisco Barros, Pilar de la Peña, Luisa María Sierra
Besides their crucial role in cell electrogenesis and maintenance of basal membrane potential, the voltage-dependent K+ channel Kv11.1/hERG1 shows an essential impact in cell proliferation and other processes linked to the maintenance of tumour phenotype. To check the possible influence of channel expression on DNA damage responses, HEK293 cells, treated with the genotoxic agent methyl methanesulfonate
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A novel mutation in KCNH2 yields loss-of-function of hERG potassium channel in long QT syndrome 2 Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-15 Kai Gu, Duoduo Qian, Huiyuan Qin, Chang Cui, W. C. Hewith A. Fernando, Daowu Wang, Juejin Wang, Kejiang Cao, Minglong Chen
Mutations in hERG (human ether-à-go-go-related gene) potassium channel are closely associated with long QT syndromes. By direct Sanger sequencing, we identified a novel KCNH2 mutation W410R in the patient with long QT syndrome 2 (LQT2). However, the electrophysiological functions of this mutation remain unknown. In comparison to hERGWT channels, hERGW410R channels have markedly decreased total and
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Vascular and haemodynamic issues of brain ageing Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-13 Lucy Beishon, Rebecca H. Clough, Meeriam Kadicheeni, Tamara Chithiramohan, Ronney B. Panerai, Victoria J. Haunton, Jatinder S. Minhas, Thompson G. Robinson
The population is ageing worldwide, thus increasing the burden of common age-related disorders to the individual, society and economy. Cerebrovascular diseases (stroke, dementia) contribute a significant proportion of this burden and are associated with high morbidity and mortality. Thus, understanding and promoting healthy vascular brain ageing are becoming an increasing priority for healthcare systems
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Decreased KLHL3 expression is involved in the activation of WNK-OSR1/SPAK-NCC cascade in type 1 diabetic mice Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-11 Qin Guo, Ya Zhang, Geng-Ru Jiang, Chong Zhang
Familial hyperkalemic hypertension (FHHt; also called pseudohypoaldosteronism type II) is a hereditary hypertensive disease which can be caused by mutations in four genes: WNK1 [with no lysine (K) 1], WNK4, Kelch-like3 (KLHL3), and cullin3 (CUL3). Decreased KLHL3 expression was identified as being involved in the pathogenesis of FHHt caused by cullin 3 disease mutations. Recent studies have revealed
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MicroRNA-1246 regulates proliferation, invasion, and differentiation in human vascular smooth muscle cells by targeting cystic fibrosis transmembrane conductance regulator (CFTR) Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-08 Diguang Pan, Guiyong Liu, Bin Li, Jingbo Jiang, Wei Chen, Wei Li, Lin Zhang, Yubao Hu, Shuyun Xie, Huayun Yang
MicroRNA (miRNA) plays a key role in the proliferation and invasion of vascular smooth muscle cells (VSMCs). However, the role and underlying mechanism of miRNAs in VSMCs are not fully understood. Therefore, this study was designed to investigate the role and mechanism of microRNA-1246 (miR-1246) in VSMCs. VSMCs were cultured, and the proliferation of VSMCs was stimulated by platelet-derived growth
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Increasing whole-body energetic stress does not augment fasting-induced changes in human skeletal muscle Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-08 Hashim Islam, Alessandra Amato, Jacob T. Bonafiglia, Fasih A. Rahman, Nicholas Preobrazenski, Andrew Ma, Craig A. Simpson, Joe Quadrilatero, Brendon J. Gurd
Fasting rapidly (≤ 6 h) activates mitochondrial biogenic pathways in rodent muscle, an effect that is absent in human muscle following prolonged (10–72 h) fasting. We tested the hypotheses that fasting-induced changes in human muscle occur shortly after food withdrawal and are modulated by whole-body energetic stress. Vastus lateralis biopsies were obtained from ten healthy males before, during (4 h)
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The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-07 Mu Chen, Yudong Fei, Tai-Zhong Chen, Yi-Gang Li, Peng-Sheng Chen
Apamin-sensitive small-conductance calcium-activated potassium (SK) current (IKAS) plays an important role in cardiac repolarization under a variety of physiological and pathological conditions. The regulation of cardiac IKAS relies on SK channel expression, intracellular Ca2+, and interaction between SK channel and intracellular Ca2+. IKAS activation participates in multiple types of arrhythmias,
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The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-06 Shanna Hamilton, Roland Veress, Andriy Belevych, Dmitry Terentyev
Sudden cardiac death due to malignant ventricular arrhythmias remains the major cause of mortality in the postindustrial world. Defective intracellular Ca2+ homeostasis has been well established as a key contributing factor to the enhanced propensity for arrhythmia in acquired cardiac disease, such as heart failure or diabetic cardiomyopathy. More recent advances provide a strong basis to the emerging
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Mechanisms underlying pathological Ca 2+ handling in diseases of the heart Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-05 Satadru K. Lahiri, Yuriana Aguilar-Sanchez, Xander H. T. Wehrens
Cardiomyocyte contraction relies on precisely regulated intracellular Ca2+ signaling through various Ca2+ channels and transporters. In this article, we will review the physiological regulation of Ca2+ handling and its role in maintaining normal cardiac rhythm and contractility. We discuss how inherited variants or acquired defects in Ca2+ channel subunits contribute to the development or progression
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Excitation-contraction coupling and calcium release in atrial muscle Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-05 L. A. Blatter, G. Kanaporis, E. Martinez-Hernandez, Y. Oropeza-Almazan, K. Banach
In cardiac muscle, the process of excitation-contraction coupling (ECC) describes the chain of events that links action potential induced myocyte membrane depolarization, surface membrane ion channel activation, triggering of Ca2+ induced Ca2+ release from the sarcoplasmic reticulum (SR) Ca2+ store to activation of the contractile machinery that is ultimately responsible for the pump function of the
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Pathological activation of CaMKII induces arrhythmogenicity through TRPM4 overactivation Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-04 Yaopeng Hu, Daniela Ross Kaschitza, Maria Essers, Prakash Arullampalam, Takayuki Fujita, Hugues Abriel, Ryuji Inoue
TRPM4 is a Ca2+-activated nonselective cation channel involved in cardiovascular physiology and pathophysiology. Based on cellular experiments and numerical simulations, the present study aimed to explore the potential arrhythmogenicity of CaMKII-mediated TRPM4 channel overactivation linked to Ca2+ dysregulation in the heart. The confocal immunofluorescence microscopy, western blot, and proximity ligation
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Cardiac adaptation and cardioprotection against arrhythmias and ischemia-reperfusion injury in mammalian hibernators Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-04 Lai-Hua Xie, Judith K. Gwathmey, Zhenghang Zhao
Hibernation allows animals to enter an energy conserving state to survive severe drops in external temperatures and a shortage of food. It has been observed that the hearts of mammalian hibernators exhibit intrinsic protection against ischemia-reperfusion (I/R) injury and cardiac arrhythmias in the winter whether they are hibernating or not. However, the molecular and ionic mechanisms for cardioprotection
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Soluble αKlotho downregulates Orai1-mediated store-operated Ca 2+ entry via PI3K-dependent signaling Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-02 Ji-Hee Kim, Eun Young Park, Kyu-Hee Hwang, Kyu-Sang Park, Seong Jin Choi, Seung-Kuy Cha
αKlotho is a type 1 transmembrane anti-aging protein. αKlotho-deficient mice have premature aging phenotypes and an imbalance of ion homeostasis including Ca2+ and phosphate. Soluble αKlotho is known to regulate multiple ion channels and growth factor-mediated phosphoinositide-3-kinase (PI3K) signaling. Store-operated Ca2+ entry (SOCE) mediated by pore-forming subunit Orai1 and ER Ca2+ sensor STIM1
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TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2021-01-02 Carolin Schilpp, Robin Lochbaum, Peter Braubach, Danny Jonigk, Manfred Frick, Paul Dietl, Oliver H. Wittekindt
TGF-β1 is a major mediator of airway tissue remodelling during atopic asthma and affects tight junctions (TJs) of airway epithelia. However, its impact on TJs of ciliated epithelia is sparsely investigated. Herein we elaborated effects of TGF-β1 on TJs of primary human bronchial epithelial cells. We demonstrate that TGF-β1 activates TGF-β1 receptors TGFBR1 and TGFBR2 resulting in ALK5-mediated phosphorylation
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Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-12-17 Barbara Peixoto Pinheiro, Barbara Vona, Hubert Löwenheim, Lukas Rüttiger, Marlies Knipper, Youssef Adel
Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance
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β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-19 Abdulaziz A. Alzahrani, Lily L. Cao, Hayyaf S. Aldossary, Demitris Nathanael, Jiarong Fu, Clare J. Ray, Keith L. Brain, Prem Kumar, Andrew M. Coney, Andrew P. Holmes
Carotid body (CB) hyperactivity promotes hypertension in response to chronic intermittent hypoxia (CIH). The plasma concentration of adrenaline is reported to be elevated in CIH and our previous work suggests that adrenaline directly activates the CB. However, a role for chronic adrenergic stimulation in mediating CB hyperactivity is currently unknown. This study evaluated whether beta-blocker treatment
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Human-induced pluripotent stem cells as models for rare cardiovascular diseases: from evidence-based medicine to precision medicine Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-18 Ziwei Pan, Antje Ebert, Ping Liang
Rare cardiovascular diseases (RCDs) refer to those cardiovascular diseases that display a low prevalence as well as morbidity. Due to the vast variety of underlying genetic mutations and the relatively low patient population, RCDs present additional challenges for diagnosis. Precision medicine may offer opportunities for designing patient-specific therapies in particular for carriers of variants with
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The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-17 Jonathan M. Whittamore, Marguerite Hatch
The membrane-bound transport proteins responsible for oxalate secretion across the large intestine remain unidentified. The apical chloride/bicarbonate (Cl−/HCO3−) exchanger encoded by Slc26a6, known as PAT-1 (putative anion transporter 1), is a potential candidate. In the small intestine, PAT-1 makes a major contribution to oxalate secretion but whether this role extends into the large intestine has
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MiRNA-190 exerts neuroprotective effects against ischemic stroke through Rho/Rho-kinase pathway Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-16 Chuan Jiang, Ning Dong, Jianli Feng, Maolin Hao
Ischemic stroke is an urgent public health concern and one of the major causes of deaths and disabilities over the world. MicroRNA (miRNA) has become a key mediator of cerebral ischemia-reperfusion (I/R) injuries. However, whether miR-190 is involved in cerebral I/R-induced neuronal damage remains unknown. This study was to investigate the role of miR-190 in the brain I/R injury. We divided the rats
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Deletion of the transcription factor Prox-1 specifically in the renal distal convoluted tubule causes hypomagnesemia via reduced expression of TRPM6 and NCC Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-16 Christina Schnoz, Sandra Moser, Denise V. Kratschmar, Alex Odermatt, Dominique Loffing-Cueni, Johannes Loffing
The renal distal convoluted tubule (DCT) is critical for the fine-tuning of urinary ion excretion and the control of blood pressure. Ion transport along the DCT is tightly controlled by posttranscriptional mechanisms including a complex interplay of kinases, phosphatases, and ubiquitin ligases. Previous work identified the transcription factor Prox-1 as a gene significantly enriched in the DCT of adult
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Correction to: Is the understanding of V̇O 2 kinetics biased by the first-order multi-exponential model? Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-12 Luis Antonio Pereira de Lima, Ricardo Dantas de Lucas, Maxime Raison, Sofiane Achiche
The original article was published with an error. The corresponding author’s email address was missing during the online publication. The email address is presented here. The Original article has been corrected.
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Editing of the myosin phosphatase regulatory subunit suppresses angiotensin II induced hypertension via sensitization to nitric oxide mediated vasodilation Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-04 Myo Htet, Jeanine A. Ursitti, Ling Chen, Steven A. Fisher
Alternative splicing of exon 24 (E24) of the myosin phosphatase regulatory subunit (Mypt1) tunes smooth muscle sensitivity to NO/cGMP-mediated vasorelaxation and thereby controls blood pressure (BP) in otherwise normal mice. This occurs via the toggling in or out of a C-terminal leucine zipper (LZ) motif required for hetero-dimerization with and activation by cGMP-dependent protein kinase cGK1α. Here
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Perfluorocarbon-based oxygen carriers: from physics to physiology Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-03 Johannes Jägers, Anna Wrobeln, Katja B. Ferenz
Developing biocompatible, synthetic oxygen carriers is a consistently challenging task that researchers have been pursuing for decades. Perfluorocarbons (PFC) are fascinating compounds with a huge capacity to dissolve gases, where the respiratory gases are of special interest for current investigations. Although largely chemically and biologically inert, pure PFCs are not suitable for injection into
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Bed nucleus of the stria terminalis modulates baroreflex cardiac activity: an interaction between alpha-1 receptors and NMDA/nitric oxide pathway Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-11-02 Davi C. Lagatta, Luciana B. Kuntze, Daniela L. Uliana, Anna B. Borges-Assis, Leonardo B. M. Resstel
The bed nucleus of the stria terminalis (BNST) is a forebrain structure, involved in the modulation of neuroendocrine, cardiovascular and autonomic responses. One of the responses is baroreflex activity, which consists in a neural mechanism responsible for keeping the blood pressure within a narrow range of variation. It has been reported that blockade of BNST α1-adrenoceptors increased the bradycardic
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Alcohol metabolite acetic acid activates BK channels in a pH-dependent manner and decreases calcium oscillations and exocytosis of secretory granules in rat pituitary GH3 cells Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-28 Ilnar Shaidullov, Elizaveta Ermakova, Aisylu Gaifullina, Anna Mosshammer, Aleksey Yakovlev, Thomas M. Weiger, Anton Hermann, Guzel Sitdikova
Acetaldehyde and acetic acid/acetate, the active metabolites of alcohol (ethanol, EtOH), generate actions of their own ranging from behavioral, physiological, to pathological/cancerogenic effects. EtOH and acetaldehyde have been studied to some depth, whereas the effects of acetic acid have been less well explored. In this study, we investigated the effect of acetic acid on big conductance calcium-activated
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Acute reversible SERCA blockade facilitates or blocks exocytosis, respectively in mouse or bovine chromaffin cells Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-27 Carmen Martínez-Ramírez, Irene Gil-Gómez, Antonio M. G. de Diego, Antonio G. García
Pre-blockade of the sarco-endoplasmic reticulum (ER) calcium ATPase (SERCA) with irreversible thapsigargin depresses exocytosis in adrenal bovine chromaffin cells (BCCs). Distinct expression of voltage-dependent Ca2+-channel subtypes and of the Ca2+-induced Ca2+ release (CICR) mechanism in BCCs versus mouse chromaffin cells (MCCs) has been described. We present a parallel study on the effects of the
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Primary culture of the rat spinal dorsal horn: a tool to investigate the effects of inflammatory stimulation on the afferent somatosensory system Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-24 Stephan Leisengang, Franz Nürnberger, Daniela Ott, Jolanta Murgott, Rüdiger Gerstberger, Christoph Rummel, Joachim Roth
One maladaptive consequence of inflammatory stimulation of the afferent somatosensory system is the manifestation of inflammatory pain. We established and characterized a neuroglial primary culture of the rat superficial dorsal horn (SDH) of the spinal cord to test responses of this structure to neurochemical, somatosensory, or inflammatory stimulation. Primary cultures of the rat SDH consist of neurons
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Disease-associated HCN4 V759I variant is not sufficient to impair cardiac pacemaking Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-23 Nadine Erlenhardt, Olaf Kletke, Franziska Wohlfarth, Marlene A. Komadowski, Lukas Clasen, Hisaki Makimoto, Susanne Rinné, Malte Kelm, Christiane Jungen, Niels Decher, Christian Meyer, Nikolaj Klöcker
The hyperpolarization-activated cation current If is a key determinant for cardiac pacemaker activity. It is conducted by subunits of the hyperpolarization-activated cyclic nucleotide–gated (HCN) channel family, of which HCN4 is predominant in mammalian heart. Both loss-of-function and gain-of-function mutations of the HCN4 gene are associated with sinus node dysfunction in humans; however, their functional
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Multisite phosphorylation of the cardiac ryanodine receptor: a random or coordinated event? Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-19 Jana Gaburjakova, Eva Krejciova, Marta Gaburjakova
Many proteins are phosphorylated at more than one phosphorylation site to achieve precise tuning of protein function and/or integrate a multitude of signals into the activity of one protein. Increasing the number of phosphorylation sites significantly broadens the complexity of molecular mechanisms involved in processing multiple phosphorylation sites by one or more distinct kinases. The cardiac ryanodine
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Platinum accumulation in the brain and alteration in the central regulation of cardiovascular and respiratory functions in oxaliplatin-treated rats Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-19 Ahmed A. Rahman, Vanesa Stojanovska, Paul Pilowsky, Kulmira Nurgali
Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. Neurotoxicity is one of its major adverse effects that often demands dose limitation. However, the effects of chronic oxaliplatin on the toxicity of the autonomic nervous system regulating cardiorespiratory function and adaptive reflexes are unknown. Male Sprague Dawley rats were treated with intraperitoneal
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Neurogenic tachykinin mechanisms in experimental nephritis of rats Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-17 Kristina Rodionova, Karl F. Hilgers, Eva-Maria Paulus, Gisa Tiegs, Christian Ott, Roland Schmieder, Mario Schiffer, Kerstin Amann, Roland Veelken, Tilmann Ditting
We demonstrated earlier that renal afferent pathways combine very likely “classical” neural signal transduction to the central nervous system and a substance P (SP)–dependent mechanism to control sympathetic activity. SP content of afferent sensory neurons is known to mediate neurogenic inflammation upon release. We tested the hypothesis that alterations in SP-dependent mechanisms of renal innervation
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TRPM4 non-selective cation channel in human atrial fibroblast growth Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-13 Christophe Simard, Christophe Magaud, Racim Adjlane, Quentin Dupas, Laurent Sallé, Alain Manrique, Patrick Bois, Jean-François Faivre, Romain Guinamard
Cardiac fibroblasts play an important role in cardiac matrix turnover and are involved in cardiac fibrosis development. Ca2+ is a driving belt in this phenomenon. This study evaluates the functional expression and contribution of the Ca2+-activated channel TRPM4 in atrial fibroblast phenotype. Molecular and electrophysiological investigations were conducted in human atrial fibroblasts in primary culture
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Advanced real-time recordings of neuronal activity with tailored patch pipettes, diamond multi-electrode arrays and electrochromic voltage-sensitive dyes Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-13 Bernd Kuhn, Federico Picollo, Valentina Carabelli, Giorgio Rispoli
To understand the working principles of the nervous system is key to figure out its electrical activity and how this activity spreads along the neuronal network. It is therefore crucial to develop advanced techniques aimed to record in real time the electrical activity, from compartments of single neurons to populations of neurons, to understand how higher functions emerge from coordinated activity
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Impaired thermoregulation in spontaneously hypertensive rats during physical exercise is related to reduced hypothalamic neuronal activation Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-10 Lucas Rios Drummond, Helton Oliveira Campos, Paulo Marcelo de Andrade Lima, Cletiana Gonçalves da Fonseca, Ana Cançado Kunstetter, Quezia Teixeira Rodrigues, Raphael Escorsim Szawka, Antônio José Natali, Thales Nicolau Prímola-Gomes, Samuel Penna Wanner, Cândido Celso Coimbra
This study aimed to evaluate the physical exercise-induced neuronal activation in brain nuclei controlling thermoregulatory responses in hypertensive and normotensive rats. Sixteen-week-old male normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs) were implanted with an abdominal temperature sensor. After recovery, the animals were subjected to a constant-speed treadmill running
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Inhibition of big-conductance Ca 2+ -activated K + channels in cerebral artery (vascular) smooth muscle cells is a major novel mechanism for tacrolimus-induced hypertension Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-08 Qiang Tang, Yun-Min Zheng, Tengyao Song, Jorge Reyes-García, Chen Wang, Yong-Xiao Wang
Tacrolimus (TAC, also called FK506), a common immunosuppressive drug used to prevent allograft rejection in transplant patients, is well known to alter the functions of blood vessels. In this study, we sought to determine whether chronic treatment of TAC could inhibit the activity of big-conductance Ca2+-activated K+ (BK) channels in vascular smooth muscle cells (SMCs), leading to hypertension. Our
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An alternative pathway for sweet sensation: possible mechanisms and physiological relevance Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-08 Elena von Molitor, Katja Riedel, Michael Krohn, Rüdiger Rudolf, Mathias Hafner, Tiziana Cesetti
Sweet substances are detected by taste-bud cells upon binding to the sweet-taste receptor, a T1R2/T1R3 heterodimeric G protein-coupled receptor. In addition, experiments with mouse models lacking the sweet-taste receptor or its downstream signaling components led to the proposal of a parallel “alternative pathway” that may serve as metabolic sensor and energy regulator. Indeed, these mice showed residual
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Intracellular activation of full-length human TREK-1 channel by hypoxia, high lactate, and low pH denotes polymodal integration by ischemic factors Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-06 Sourajit Mukherjee, Sujit Kumar Sikdar
TREK-1, a two-pore domain potassium channel, responds to ischemic levels of intracellular lactate and acidic pH to provide neuroprotection. There are two splice variants of hTREK1: the shorter splice variant having a shorter N-terminus compared with the full-length hTREK1 with similar C-terminus sequence that is widely expressed in the brain. The shorter variant was reported to be irresponsive to hypoxia—a
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Correction to: TRPM7 channel activity in Jurkat T lymphocytes during magnesium depletion and loading: implications for divalent metal entry and cytotoxicity Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-10-02 Alayna Mellott, Jananie Rockwood, Tetyana Zhelay, Charles Tuan Luu, Taku Kaitsuka, J. Ashot Kozak
The original article was published with an error. In Figure 9b there are 3 typographical errors: instead of the Greek mu letter it shows the unconverted data.
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Astroglial asthenia and loss of function, rather than reactivity, contribute to the ageing of the brain. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-26 Alexei Verkhratsky,Marcus Augusto-Oliveira,Augustas Pivoriūnas,Alexander Popov,Alexey Brazhe,Alexey Semyanov
Astroglia represent a class of heterogeneous, in form and function, cells known as astrocytes, which provide for homoeostasis and defence of the central nervous system (CNS). Ageing is associated with morphological and functional remodelling of astrocytes with a prevalence of morphological atrophy and loss of function. In particular, ageing is associated with (i) decrease in astroglial synaptic coverage
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TRPM7 channel activity in Jurkat T lymphocytes during magnesium depletion and loading: implications for divalent metal entry and cytotoxicity. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-22 Alayna Mellott,Jananie Rockwood,Tetyana Zhelay,Charles Tuan Luu,Taku Kaitsuka,J Ashot Kozak
TRPM7 is a cation channel-protein kinase highly expressed in T lymphocytes and other immune cells. It has been proposed to constitute a cellular entry pathway for Mg2+ and divalent metal cations such as Ca2+, Zn2+, Cd2+, Mn2+, and Ni2+. TRPM7 channels are inhibited by cytosolic Mg2+, rendering them largely inactive in intact cells. The dependence of channel activity on extracellular Mg2+ is less well
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Cellular and systemic mechanisms for glucose sensing and homeostasis. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-22 Jong-Woo Sohn,Won-Kyung Ho
Glucose is a major source of energy in animals. Maintaining blood glucose levels within a physiological range is important for facilitating glucose uptake by cells, as required for optimal functioning. Glucose homeostasis relies on multiple glucose-sensing cells in the body that constantly monitor blood glucose levels and respond accordingly to adjust its glycemia. These include not only pancreatic
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TRPV4 and TRPM8 as putative targets for chronic low back pain alleviation. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-21 Stefania Fozzato,Nicolò Baranzini,Elena Bossi,Raffaella Cinquetti,Annalisa Grimaldi,Paola Campomenosi,Michele Francesco Surace
The purpose of this study is to investigate the presence of nervous fibers and expression of TRP channels in samples harvested during decompressive/fusion spine surgeries from patients affected by chronic low back pain (CLBP). The aim was to understand if members of this family of receptors played a role in detection and processing of painful stimuli, to eventually define them as potential targets
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Functional interactions between complex I and complex II with nNOS in regulating cardiac mitochondrial activity in sham and hypertensive rat hearts. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-17 Yu Na Wu,Vidya K Sudarshan,Shi Chao Zhu,Yong Feng Shao,Sung Joon Kim,Yin Hua Zhang
Nitric oxide (NO) affects mitochondrial activity through its interactions with complexes. Here, we investigated regulations of complex I (C-I) and complex II (C-II) by neuronal NO synthase (nNOS) in the presence of fatty acid supplementation and the impact on left ventricular (LV) mitochondrial activity from sham and angiotensin II (Ang-II)–induced hypertensive (HTN) rats. Our results showed that nNOS
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Elevated ROS depress mitochondrial oxygen utilization efficiency in cardiomyocytes during acute hypoxia. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-17 Ru-Zhou Zhao,Xiao-Bo Wang,Shuai Jiang,Ning-Yu Ru,Bo Jiao,Yun-Ying Wang,Zhi-Bin Yu
Mitochondria are important sites for the production of ATP and the generation of ROS in cells. However, whether acute hypoxia increases ROS generation in cells or affects ATP production remains unclear, and therefore, monitoring the changes in ATP and ROS in living cells in real time is important. In this study, cardiomyocytes were transfected with RoGFP for ROS detection and MitGO-Ateam2 for ATP detection
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GDF15, an update of the physiological and pathological roles it plays: a review. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-16 Artin Assadi,Azadeh Zahabi,Robert A Hart
Growth differentiation factor 15 (GDF15) is a peptide hormone, and a divergent member of the transforming growth factor beta (TGFβ) superfamily. In normal physiology, GDF15 is expressed in multiple tissues at a low concentration. GDF15 is overexpressed during and following many pathological conditions such as tissue injury and inflammation in order to play a protective role. However, GDF15 appears
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Taste transduction and channel synapses in taste buds. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-16 Akiyuki Taruno,Kengo Nomura,Tsukasa Kusakizako,Zhongming Ma,Osamu Nureki,J Kevin Foskett
The variety of taste sensations, including sweet, umami, bitter, sour, and salty, arises from diverse taste cells, each of which expresses specific taste sensor molecules and associated components for downstream signal transduction cascades. Recent years have witnessed major advances in our understanding of the molecular mechanisms underlying transduction of basic tastes in taste buds, including the
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Differential modulation of active expiration during hypercapnia by the medullary raphe in unanesthetized rats. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-11 Isabela P Leirão,Daniel B Zoccal,Luciane H Gargaglioni,Glauber S F da Silva
Active expiration represents an important mechanism to improve ventilation in conditions of augmented ventilatory demand, such as hypercapnia. While a rostral ventromedullary region, the parafacial respiratory group (pFRG), has been identified as a conditional expiratory oscillator, little is known about how central chemosensitive sites contribute to modulate active expiration under hypercapnia. In
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Interleukin-1β in hypothalamic paraventricular nucleus mediates excitatory renal reflex. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-11 Fen Zheng,Chao Ye,Guo-Wei Wan,Bing Zhou,Ying Tong,Jian-Zhen Lei,Qi Chen,Yue-Hua Li,Yu-Ming Kang,Guo-Qing Zhu
Chemical stimulation of kidney causes sympathetic activation and pressor responses in rats. The excitatory renal reflex (ERR) is mediated by angiotensin type 1 receptor (AT1R) and superoxide anions in hypothalamic paraventricular nucleus (PVN). The aim of this study is to determine whether interleukin-1β (IL-1β) in the PVN mediates the ERR, and whether the IL-1β production in the PVN is dependent on
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Activation of farnesoid X receptor (FXR) induces crystallin zeta expression in mouse medullary collecting duct cells. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-10 Gulzar Alam,Zhilin Luan,Aneesa Gul,Heyuan Lu,Yunfeng Zhou,Xiaoxiao Huo,Yaqing Li,Chunxiu Du,Zhaokang Luo,Haibo Zhang,Hu Xu,Feng Zheng,Youfei Guan,Xiaoyan Zhang
Crystallin zeta (CRYZ) is a phylogenetically restricted water-soluble protein and provides cytoprotection against oxidative stress via multiple mechanisms. Increasing evidence suggests that CRYZ is high abundantly expressed in the kidney where it acts as a transacting factor in increasing glutaminolysis and the Na+/K+/2Cl– cotransporter (BSC1/NKCC2) expression to help maintain acid–base balance and
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Correction to: Preclinical pharmacological in vitro investigations on low chloride conductance myotonia: effects of potassium regulation. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-03 Kerstin Hoppe,Sunisa Chaiklieng,Frank Lehmann-Horn,Karin Jurkat-Rott,Scott Wearing,Werner Klingler
The original article contains an error during online publication. Table 2 was included during production round and now deleted. The Original article has been corrected.
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Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-01 Joseph Brook,Min-Young Kim,Simos Koutsoftidis,David Pitcher,Danya Agha-Jaffar,Annam Sufi,Catherine Jenkins,Konstantinos Tzortzis,Suofeiya Ma,Richard J Jabbour,Charles Houston,Balvinder S Handa,Xinyang Li,Ji-Jian Chow,Anand Jothidasan,Poppy Bristow,Justin Perkins,Sian Harding,Anil A Bharath,Fu Siong Ng,Nicholas S Peters,Chris D Cantwell,Rasheda A Chowdhury
We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological
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Expression of serotonin receptor HTR4 in glucagon-like peptide-1-positive enteroendocrine cells of the murine intestine. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-09-01 Motoshi Okumura,Akihiro Hamada,Fumina Ohsaka,Takeshi Tsuruta,Tohru Hira,Kei Sonoyama
Serotonin (5-hydroxytryptamine [5-HT]) synthesized and released in enterochromaffin (EC) cells participates in various functions in the gastrointestinal tract by acting on a diverse range of 5-HT receptors (HTRs) expressed on smooth muscle, enteric neurons, and epithelial cells. We previously observed that genes encoding HTR2A, HTR2B, and HTR4 are expressed in murine intestinal organoids, suggesting
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Structure, function and regulation of mammalian glucose transporters of the SLC2 family Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-06-26 Geoffrey D. Holman
The SLC2 genes code for a family of GLUT proteins that are part of the major facilitator superfamily (MFS) of membrane transporters. Crystal structures have recently revealed how the unique protein fold of these proteins enables the catalysis of transport. The proteins have 12 transmembrane spans built from a replicated trimer substructure. This enables 4 trimer substructures to move relative to each
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Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-06-26 Alexandra Chadt, Hadi Al-Hasani
A family of facilitative glucose transporters (GLUTs) is involved in regulating tissue-specific glucose uptake and metabolism in the liver, skeletal muscle, and adipose tissue to ensure homeostatic control of blood glucose levels. Reduced glucose transport activity results in aberrant use of energy substrates and is associated with insulin resistance and type 2 diabetes. It is well established that
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Plant glucose transporter structure and function. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-08-26 Dietmar Geiger
The carbohydrate D-glucose is the main source of energy in living organisms. In contrast to animals, as well as most fungi, bacteria, and archaea, plants are capable to synthesize a surplus of sugars characterizing them as autothrophic organisms. Thus, plants are de facto the source of all food on earth, either directly or indirectly via feed to livestock. Glucose is stored as polymeric glucan, in
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Glucose transporters in the small intestine in health and disease. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-08-23 Hermann Koepsell
Absorption of monosaccharides is mainly mediated by Na+-d-glucose cotransporter SGLT1 and the facititative transporters GLUT2 and GLUT5. SGLT1 and GLUT2 are relevant for absorption of d-glucose and d-galactose while GLUT5 is relevant for d-fructose absorption. SGLT1 and GLUT5 are constantly localized in the brush border membrane (BBM) of enterocytes, whereas GLUT2 is localized in the basolateral membrane
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Spontaneous recovery, time course, and circadian influence on habituation of the cardiovascular responses to repeated restraint stress in rats. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-08-22 Carlos E Santos,Ricardo Benini,Carlos C Crestani
We investigated the spontaneous recovery, time course, and the influence of the time of day on the habituation of the cardiovascular responses with repeated exposure to restraint stress in male rats. Habituation of the corticosterone response to repeated restraint stress was also evaluated. The circulating corticosterone response decreased during both the stress and recovery periods of the tenth session
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Dopamine D4 receptor subtype activation reduces the rat cardiac parasympathetic discharge. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-08-21 José Ángel García-Pedraza,Asunción Morán,María Luisa Martín,Claudia Ollauri-Ibáñez,Alicia Rodríguez-Barbero,Carlos M Villalón,Mónica García-Domingo
The dopaminergic system influences the heart rhythm by inhibiting the rat cardiac sympathetic and parasympathetic neurotransmissions through activation of D2-like receptors (encompassing the D2, D3, and D4 subtypes). Whereas D2 receptor subtype activation results in cardiac sympatho-inhibition, the dopamine receptor subtypes involved in rat cardiac vago-inhibition remain unknown. Hence, this study
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SGLT2 and cancer. Pflugers Arch. Eur. J. Physiol. (IF 3.158) Pub Date : 2020-08-20 Ernest M Wright
Glycolysis plays a central role in tumor metabolism and growth, and this is reflected in a high rate of glucose uptake. It is commonly assumed that the upregulation of the facilitated glucose transporter GLUT1 meets the tumor’s demand for sugar. This underlies the success in using 2FDG PET imaging in the clinic to identify and stage many tumors. However, 2FDG is not a substrate for a second class of