Sirtuin 1 and endothelial glycocalyx.
Abstract Sirtuin1 deficiency or reduced activity comprises one of the hallmarks of diseases as diverse as chronic cardiovascular, renal, and metabolic, some malignancies, and infections, as well as aging-associated diseases. In a mouse model of endothelium-limited defect in sirtuin 1 deacetylase activity, we found a dramatic reduction in the volume of endothelial glycocalyx. This was associated with the surge in the levels of one of key scaffolding heparan sulfate proteoglycans of endothelial glycocalyx, syndecan-4, and specifically, its extracellular domain (ectodomain). We found that the defect in endothelial si...
Source: Pflugers Archiv : European Journal of Physiology - June 3, 2020 Category: Physiology Authors: Lipphardt M, Song JW, Goligorsky MS Tags: Pflugers Arch Source Type: research

Defective autophagy in vascular smooth muscle cells increases passive stiffness of the mouse aortic vessel wall.
Abstract Aging and associated progressive arterial stiffening are both important predictors for the development of cardiovascular diseases. Recent evidence showed that autophagy, a catabolic cellular mechanism responsible for nutrient recycling, plays a major role in the physiology of vascular cells such as endothelial cells and vascular smooth muscle cells (VSMCs). Moreover, several autophagy inducing compounds are effective in treating arterial stiffness. Yet, a direct link between VSMC autophagy and arterial stiffness remains largely unidentified. Therefore, we investigated the effects of a VSMC-specific deleti...
Source: Pflugers Archiv : European Journal of Physiology - June 2, 2020 Category: Physiology Authors: De Munck DG, Leloup AJA, De Meyer GRY, Martinet W, Fransen P Tags: Pflugers Arch Source Type: research

Gerhard Giebisch (1927-2020): a pioneer of kidney physiology.
PMID: 32483724 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - June 1, 2020 Category: Physiology Authors: Murer H, Wagner CA Tags: Pflugers Arch Source Type: research

Erythroid glucose transport in health and disease.
Abstract Glucose transport is intimately linked to red blood cell physiology. Glucose is the unique energy source for these cells, and defects in glucose metabolism or transport activity are associated with impaired red blood cell morphology and deformability leading to reduced lifespan. In vertebrate erythrocytes, glucose transport is mediated by GLUT1 (in humans) or GLUT4 transporters. These proteins also account for dehydroascorbic acid (DHA) transport through erythrocyte membrane. The peculiarities of glucose transporters and the red blood cell pathologies involving GLUT1 are summarized in the present review. ...
Source: Pflugers Archiv : European Journal of Physiology - May 30, 2020 Category: Physiology Authors: Guizouarn H, Allegrini B Tags: Pflugers Arch Source Type: research

TASK channels: channelopathies, trafficking, and receptor-mediated inhibition.
Abstract TWIK-related acid-sensitive K+ (TASK) channels contribute to the resting membrane potential in various kinds of cells, such as brain neurons, smooth muscle cells, and endocrine cells. Loss-of-function mutations at multiple sites in the KCNK3 gene encoding for TASK1 channels are one of the causes of pulmonary arterial hypertension in humans, whereas a mutation at only one site is reported for TASK3 channels, resulting in a syndrome of mental retardation, hypotonia, and facial dysmorphism. TASK channels are subject to regulation by G protein-coupled receptors (GPCRs). Two mechanisms have been proposed for t...
Source: Pflugers Archiv : European Journal of Physiology - May 29, 2020 Category: Physiology Authors: Inoue M, Matsuoka H, Harada K, Mugishima G, Kameyama M Tags: Pflugers Arch Source Type: research

Olfactory signals from the main olfactory bulb converge with taste information from the chorda tympani nerve in the agranular insular cortex of rats.
We examined the spatiotemporal dynamics of cortical responses induced by stimulating the chorda tympani nerve (CT) and the main olfactory bulb (mOB) in male Sprague-Dawley rats by in vivo optical imaging with a voltage-sensitive dye (VSD). CT stimulation elicited responses in the rostral part of the dysgranular IC (DI), while responses to mOB stimulation were observed in the agranular IC (AI) as well as in the piriform cortex (PC). To characterize the temporal specificity of these responses, we performed combined mOB and CT stimulation with three different timings: simultaneous stimulation and the stimulation of the mOB 15...
Source: Pflugers Archiv : European Journal of Physiology - May 27, 2020 Category: Physiology Authors: Mizoguchi N, Muramoto K, Kobayashi M Tags: Pflugers Arch Source Type: research

Improved adaptation to physical stress in mice overexpressing SUR2A is associated with changes in the pattern of Q-T interval.
Abstract The purpose of this study was to determine whether increased expression of SUR2A, a regulatory subunit of sarcolemmal ATP-sensitive K+ (KATP) channels, improves adaptation to physical stress and regulates cardiac electrophysiology in physical stress. All experiments have been done on transgenic mice in which SUR2A expression was controlled by cytomegalovirus immediate-early (CMV) promoter (SUR2A) and their littermate wild-type controls (WT). The levels of mRNA in heart tissue were measured by real-time RT-PCR. Electrocardiogram (ECG) was monitored with telemetry. The physical adaptation to stress was eluc...
Source: Pflugers Archiv : European Journal of Physiology - May 27, 2020 Category: Physiology Authors: Sudhir R, Du Q, Sukhodub A, Jovanović S, Jovanović A Tags: Pflugers Arch Source Type: research

Acute intracerebroventricular injection of chemerin-9 increases systemic blood pressure through activating sympathetic nerves via CMKLR1 in brain.
We examined the effects of acute i.c.v. injection of chemerin-9 (10 nmol/head) on systemic BP by a carotid cannulation method in the control or CMKLR1 small interfering (si) RNA-treated Wistar rats (0.04 nmol, 3 days, i.c.v.). We examined protein expression of CMKLR1 around brain ventricles by Western blotting. We examined the effects of acute i.c.v. injection of chemerin-9 on serum adrenaline by a high performance liquid chromatography. In the control siRNA-treated rats, chemerin-9 significantly increased mean BP, which reached a peak at 2 to 4 min after injection. On the other hand, in the CMKLR1 siRN...
Source: Pflugers Archiv : European Journal of Physiology - May 27, 2020 Category: Physiology Authors: Yamamoto A, Matsumoto K, Hori K, Kameshima S, Yamaguchi N, Okada S, Okada M, Yamawaki H Tags: Pflugers Arch Source Type: research

Cortical multisensory integration-a special role of the agranular insular cortex?
PMID: 32458084 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - May 26, 2020 Category: Physiology Authors: Brunert D, Rothermel M Tags: Pflugers Arch Source Type: research

The TRPV3 channel of the bovine rumen: localization and functional characterization of a protein relevant for ruminal ammonia transport.
Abstract Large quantities of ammonia (NH3 or NH4+) are absorbed from the gut, associated with encephalitis in hepatic disease, poor protein efficiency in livestock, and emissions of nitrogenous climate gasses. Identifying the transport mechanisms appears urgent. Recent functional and mRNA data suggest that absorption of ammonia from the forestomach of cattle may involve TRPV3 channels. The purpose of the present study was to sequence the bovine homologue of TRPV3 (bTRPV3), localize the protein in ruminal tissue, and confirm transport of NH4+. After sequencing, bTRPV3 was overexpressed in HEK-293 cells and Xenopus ...
Source: Pflugers Archiv : European Journal of Physiology - May 26, 2020 Category: Physiology Authors: Liebe F, Liebe H, Kaessmeyer S, Sponder G, Stumpff F Tags: Pflugers Arch Source Type: research

Rare CACNA1A mutations leading to congenital ataxia.
, Serrano M Abstract Human mutations in the CACNA1A gene that encodes the pore-forming α1A subunit of the voltage-gated CaV2.1 (P/Q-type) Ca2+ channel cause multiple neurological disorders including sporadic and familial hemiplegic migraine, as well as cerebellar pathologies such as episodic ataxia, progressive ataxia, and early-onset cerebellar syndrome consistent with the definition of congenital ataxia (CA), with presentation before the age of 2 years. Such a pathological role is in accordance with the physiological relevance of CaV2.1 in neuronal tissue, especially in the cerebellum. This review deals wi...
Source: Pflugers Archiv : European Journal of Physiology - May 26, 2020 Category: Physiology Authors: Izquierdo-Serra M, Fernández-Fernández JM, Serrano M Tags: Pflugers Arch Source Type: research

Distribution of the organic anion transporters Oat1 and Oat3 between renal membrane microdomains in obstructive jaundice.
Abstract Relation between the renal function and the membrane environment where the organic anion transporters Oat1 and Oat3 are localized is scarce. The aim of this study was to examine the Oat1 and Oat3 distribution in different cellular fractions under physiological conditions as well as the effects of extrahepatic cholestasis on membrane distribution of both proteins. Besides, the potential role of jaundice serum on the Oat1 and Oat3 expression in suspensions of renal tubular cells was evaluated. Cellular and membrane fractions of renal cortex were obtained from control rats to evaluate Oat1 and Oat3 protein e...
Source: Pflugers Archiv : European Journal of Physiology - May 25, 2020 Category: Physiology Authors: Nosetto EC, Campagno RV, Torres AM, Brandoni A Tags: Pflugers Arch Source Type: research

New ways for an old cation.
PMID: 32448954 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - May 25, 2020 Category: Physiology Authors: Diener M Tags: Pflugers Arch Source Type: research

TRPA1 gene variants hurting our feelings.
Abstract TRPA1 is a Ca2+-permeable, non-selective cation channel that is activated by thermal and mechanical stimuli, an amazing variety of potentially noxious chemicals, and by endogenous molecules that signal tissue injury. The expression of this channel in nociceptive neurons and epithelial cells puts it at the first line of defense and makes it a key determinant of adaptive protective behaviors. For the same reasons, TRPA1 is implicated in a wide variety of disease conditions, such as acute, neuropathic, and inflammatory pains, and is postulated to be a target for therapeutic interventions against acquired dis...
Source: Pflugers Archiv : European Journal of Physiology - May 22, 2020 Category: Physiology Authors: Naert R, Talavera A, Startek JB, Talavera K Tags: Pflugers Arch Source Type: research

Regulation of cardiovascular calcium channel activity by post-translational modifications or interacting proteins.
Abstract Voltage-gated calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alterations of calcium channel function have been implicated in multiple cardiovascular diseases, such as hypertension, atrial fibrillation, and long QT syndrome. Post-translational modifications do expand cardiovascular calcium channel structure and function to affect processes such as channel trafficking or polyubiquitination by two E3 ubiquitin ligases, Ret finger protein 2 (Rfp2) or murine double minute 2 protein (Mdm2). Additionally, biophysical property such as Ca2+-depende...
Source: Pflugers Archiv : European Journal of Physiology - May 20, 2020 Category: Physiology Authors: Loh KWZ, Liang MC, Soong TW, Hu Z Tags: Pflugers Arch Source Type: research

Cardiac and neuronal HCN channelopathies.
Abstract Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed as four different isoforms (HCN1-4) in the heart and in the central and peripheral nervous systems. In the voltage range of activation, HCN channels carry an inward current mediated by Na+ and K+, termed If in the heart and Ih in neurons. Altered function of HCN channels, mainly HCN4, is associated with sinus node dysfunction and other arrhythmias such as atrial fibrillation, ventricular tachycardia, and atrioventricular block. In recent years, several data have also shown that dysfunctional HCN channels, in particular HCN1, ...
Source: Pflugers Archiv : European Journal of Physiology - May 18, 2020 Category: Physiology Authors: Rivolta I, Binda A, Masi A, DiFrancesco JC Tags: Pflugers Arch Source Type: research

A study of the outward background current conductance gK1, the pacemaker current conductance gf, and the gap junction conductance gj as determinants of biological pacing in single cells and in a two-cell syncytium using the dynamic clamp.
Abstract We previously demonstrated that a two-cell syncytium, composed of a ventricular myocyte and an mHCN2 expressing cell, recapitulated most properties of in vivo biological pacing induced by mHCN2-transfected hMSCs in the canine ventricle. Here, we use the two-cell syncytium, employing dynamic clamp, to study the roles of gf (pacemaker conductance), gK1 (background K+ conductance), and gj (intercellular coupling conductance) in biological pacing. We studied gf and gK1 in single HEK293 cells expressing cardiac sodium current channel Nav1.5 (SCN5A). At fixed gf, increasing gK1 hyperpolarized the cell and initi...
Source: Pflugers Archiv : European Journal of Physiology - May 15, 2020 Category: Physiology Authors: Valiunas V, Cohen IS, Brink PR, Clausen C Tags: Pflugers Arch Source Type: research

Is curvature of the force-velocity relationship affected by oxygen availability? Evidence from studies in ex vivo and in situ rat muscles.
Abstract The power of shortening contractions in skeletal muscle is determined by the force-velocity relationship. Fatigue has been reported to either increase or decrease the force-velocity curvature depending on experimental circumstances. These discrepant findings may be related to experimental differences in oxygen availability. We therefore investigated how the curvature of the force-velocity relationship in soleus and gastrocnemius rat muscles is affected during fatigue, in both an ex vivo setup without an intact blood perfusion and in an in situ setup with an intact blood perfusion. Furthermore, we investig...
Source: Pflugers Archiv : European Journal of Physiology - May 15, 2020 Category: Physiology Authors: Kristensen AM, MacDougall KB, MacIntosh BR, Overgaard K Tags: Pflugers Arch Source Type: research

Pacing made easy: dynamic clamp promotes quantitative understanding of cardiac autorhythmicity and boosts the development of new pacemakers.
PMID: 32415462 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - May 15, 2020 Category: Physiology Authors: Shmygol A Tags: Pflugers Arch Source Type: research

Towards the clinical translation of optogenetic skeletal muscle stimulation.
n T Abstract Paralysis is a frequent phenomenon in many diseases, and to date, only functional electrical stimulation (FES) mediated via the innervating nerve can be employed to restore skeletal muscle function in patients. Despite recent progress, FES has several technical limitations and significant side effects. Optogenetic stimulation has been proposed as an alternative, as it may circumvent some of the disadvantages of FES enabling cell type-specific, spatially and temporally precise stimulation of cells expressing light-gated ion channels, commonly Channelrhodopsin2. Two distinct approaches for the restorati...
Source: Pflugers Archiv : European Journal of Physiology - May 15, 2020 Category: Physiology Authors: Gundelach LA, Hüser MA, Beutner D, Ruther P, Bruegmann T Tags: Pflugers Arch Source Type: research

Altered functional properties of a missense variant in the TRESK K+ channel (KCNK18) associated with migraine and intellectual disability.
Abstract Mutations in the KCNK18 gene that encodes the TRESK K2P potassium channel have previously been linked with typical familial migraine with aura. Recently, an atypical clinical case has been reported in which a male individual carrying the p.Trp101Arg (W101R) missense mutation in the KCNK18 gene was diagnosed with intellectual disability and migraine with brainstem aura. Here we report the functional characterization of this new missense variant. This mutation is located in a highly conserved residue close to the selectivity filter, and our results show although these mutant channels retain their K+ selecti...
Source: Pflugers Archiv : European Journal of Physiology - May 12, 2020 Category: Physiology Authors: Imbrici P, Nematian-Ardestani E, Hasan S, Pessia M, Tucker SJ, D'Adamo MC Tags: Pflugers Arch Source Type: research

Glucose transporters in pancreatic islets.
Abstract The fine-tuning of glucose uptake mechanisms is rendered by various glucose transporters with distinct transport characteristics. In the pancreatic islet, facilitative diffusion glucose transporters (GLUTs), and sodium-glucose cotransporters (SGLTs) contribute to glucose uptake and represent important components in the glucose-stimulated hormone release from endocrine cells, therefore playing a crucial role in blood glucose homeostasis. This review summarizes the current knowledge about cell type-specific expression profiles as well as proven and putative functions of distinct GLUT and SGLT family members...
Source: Pflugers Archiv : European Journal of Physiology - May 12, 2020 Category: Physiology Authors: Berger C, Zdzieblo D Tags: Pflugers Arch Source Type: research

Impact of intracellular hemin on N-type inactivation of voltage-gated K+ channels.
SH Abstract N-type inactivation of voltage-gated K+ channels is conferred by the N-terminal "ball" domains of select pore-forming α subunits or of auxiliary β subunits, and influences electrical cellular excitability. Here, we show that hemin impairs inactivation of K+ channels formed by Kv3.4 α subunits as well as that induced by the subunits Kvβ1.1, Kvβ1.2, and Kvβ3.1 when coexpressed with α subunits of the Kv1 subfamily. In Kvβ1.1, hemin interacts with cysteine and histidine residues in the N terminus (C7 and H10) with high affinity (EC50 100 nM). Simil...
Source: Pflugers Archiv : European Journal of Physiology - May 10, 2020 Category: Physiology Authors: Coburger I, Yang K, Bernert A, Wiesel E, Sahoo N, Swain SM, Hoshi T, Schönherr R, Heinemann SH Tags: Pflugers Arch Source Type: research

A new world of heme function.
PMID: 32388730 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - May 10, 2020 Category: Physiology Authors: Kubo Y Tags: Pflugers Arch Source Type: research

Fetuin-B regulates vascular plaque rupture via TGF- β receptor-mediated Smad pathway in vascular smooth muscle cells.
Fetuin-B regulates vascular plaque rupture via TGF-β receptor-mediated Smad pathway in vascular smooth muscle cells. Pflugers Arch. 2020 May 07;: Authors: Jung SH, Lee D, Jin H, Lee HM, Ko HM, Lee KJ, Kim SJ, Ryu Y, Choi WS, Kim B, Won KJ Abstract Fetuin-B is a serum protein linked to the regulation of physiological or pathophysiological events such as fertility, energy metabolism, and liver disease. Recently, fetuin-B has been reported to be involved in the modulation of the rupture of atherosclerotic plaques associated with acute myocardial infarction. However, the exact mechanism involved in t...
Source: Pflugers Archiv : European Journal of Physiology - May 7, 2020 Category: Physiology Authors: Jung SH, Lee D, Jin H, Lee HM, Ko HM, Lee KJ, Kim SJ, Ryu Y, Choi WS, Kim B, Won KJ Tags: Pflugers Arch Source Type: research

SLC9A4 in the organum vasculosum of the lamina terminalis is a [Na+] sensor for the control of water intake.
Abstract Nax is a brain [Na+] sensor expressed in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT) in the brain. We previously demonstrated that Nax signals are involved in the control of water intake behavior through the Nax/TRPV4 pathway. Nax gene knockout mice showed significantly attenuated water intake after an intracerebroventricular (ICV) injection of a hypertonic NaCl solution; however, the induction of a certain amount of water intake still remained, suggesting that another unknown [Na+]-dependent pathway besides the Nax/TRPV4 pathway contributes to water intake. In the p...
Source: Pflugers Archiv : European Journal of Physiology - May 6, 2020 Category: Physiology Authors: Sakuta H, Lin CH, Hiyama TY, Matsuda T, Yamaguchi K, Shigenobu S, Kobayashi K, Noda M Tags: Pflugers Arch Source Type: research

Transporters of glucose and other carbohydrates in bacteria.
Abstract Glucose arguably is the most important energy carrier, carbon source for metabolites and building block for biopolymers in all kingdoms of life. The proper function of animal organs and tissues depends on the continuous supply of glucose from the bloodstream. Most animals can resorb only a small number of monosaccharides, mostly glucose, galactose and fructose, while all other sugars oligosaccharides and dietary fibers are degraded and metabolized by the microbiota of the lower intestine. Bacteria, in contrast, are omnivorous. They can import and metabolize structurally different sugars and, as a consorti...
Source: Pflugers Archiv : European Journal of Physiology - May 6, 2020 Category: Physiology Authors: Jeckelmann JM, Erni B Tags: Pflugers Arch Source Type: research

Metabolic implications of circadian disruption.
Abstract Circadian rhythms are generated by the circadian clock, a self-sustained internal timing system that exhibits 24-h rhythms in the body. In mammals, circadian rhythms are driven by a central clock located in suprachiasmatic nucleus and various peripheral clocks located in different tissues and organs of the body. Many cellular, behavioral, and physiological processes are regulated by the circadian clock in coordination with environmental cues. The process of metabolism is also under circadian regulation. Loss of synchronization between the internal clock and environmental zeitgebers results in disruption o...
Source: Pflugers Archiv : European Journal of Physiology - May 4, 2020 Category: Physiology Authors: Fatima N, Rana S Tags: Pflugers Arch Source Type: research

Skeletal muscle ClC-1 chloride channels in health and diseases.
Abstract In 1970, the study of the pathomechanisms underlying myotonia in muscle fibers isolated from myotonic goats highlighted the importance of chloride conductance for skeletal muscle function; 20 years later, the human ClC-1 chloride channel has been cloned; last year, the crystal structure of human protein has been solved. Over the years, the efforts of many researchers led to significant advances in acknowledging the role of ClC-1 in skeletal muscle physiology and the mechanisms through which ClC-1 dysfunctions lead to impaired muscle function. The wide spectrum of pathophysiological conditions associa...
Source: Pflugers Archiv : European Journal of Physiology - May 2, 2020 Category: Physiology Authors: Altamura C, Desaphy JF, Conte D, De Luca A, Imbrici P Tags: Pflugers Arch Source Type: research

Chamber-specific regulation of atrial natriuretic peptide secretion in cardiac hypertrophy: atrial wall dynamics in the ANP secretion.
Abstract The heart is involved in the regulation of blood pressure and body fluid homeostasis. As a blood volume sensor and effector for the regulation of the volume and pressure homeostasis, the atria are the central regulator to secrete humoral messenger cardiac natriuretic hormones into the circulation. The primary action of the atria in response to the volume change in the body is to control the secretion of atrial natriuretic peptide (ANP), a member of the family of cardiac natriuretic hormones. Although all cardiac chambers are able to secrete ANP, the major source of the cardiac hormone is the atria until r...
Source: Pflugers Archiv : European Journal of Physiology - May 2, 2020 Category: Physiology Authors: Lee HS, Cho KW, Kim HY, Ahn YM Tags: Pflugers Arch Source Type: research

Ketoprofen alleviates diet-induced obesity and promotes white fat browning in mice via the activation of COX-2 through mTORC1-p38 signaling pathway.
Abstract The nonsteroidal anti-inflammatory drug (NSAID) ketoprofen is commonly used as a pain reliever, but its role in mediating the energy metabolism in lipids is unclear. This paper reports for the first time the critical role of ketoprofen in ameliorating white fat browning and alleviating diet-induced obesity. The effects of ketoprofen were evaluated using C57BL/6 mice fed a high fat diet and the expression levels of the target genes and proteins in the lipid metabolisms were determined by quantitative real-time PCR, immunoblot analysis, histopathology study, immunofluorescence, and molecular docking techniq...
Source: Pflugers Archiv : European Journal of Physiology - May 1, 2020 Category: Physiology Authors: Kang NH, Mukherjee S, Jang MH, Pham HG, Choi M, Yun JW Tags: Pflugers Arch Source Type: research

Characterisation of the static offset in the travelling wave in the cochlear basal turn.
Abstract In mammals, audition is triggered by travelling waves that are evoked by acoustic stimuli in the cochlear partition, a structure containing sensory hair cells and a basilar membrane. When the cochlea is stimulated by a pure tone of low frequency, a static offset occurs in the vibration in the apical turn. In the high-frequency region at the cochlear base, multi-tone stimuli induce a quadratic distortion product in the vibrations that suggests the presence of an offset. However, vibrations below 100 Hz, including a static offset, have not been directly measured there. We therefore constructed an inter...
Source: Pflugers Archiv : European Journal of Physiology - April 22, 2020 Category: Physiology Authors: Ota T, Nin F, Choi S, Muramatsu S, Sawamura S, Ogata G, Sato MP, Doi K, Doi K, Tsuji T, Kawano S, Reichenbach T, Hibino H Tags: Pflugers Arch Source Type: research

Intracellular Cl- dysregulation causing and caused by pathogenic neuronal activity.
Abstract The intracellular Cl- concentration ([Cl-]i) is tightly regulated in brain neurons for stabilizing brain performance. The [Cl-]i in mature neurons is determined by the balance between the rate of Cl- extrusion mainly mediated by the neuron-specific type 2 K+-Cl- cotransporter (KCC2) and the rate of Cl- entry through various Cl- channels including GABAA receptors during neuronal activity. Disturbance of the balance causes instability of brain circuit performance and may lead to epileptic seizures. In the first part of this review, we discuss how genetic alterations in KCC2 in humans cause infantile migrati...
Source: Pflugers Archiv : European Journal of Physiology - April 17, 2020 Category: Physiology Authors: Akita T, Fukuda A Tags: Pflugers Arch Source Type: research

MiR-155 inhibition alleviates suppression of osteoblastic differentiation by high glucose and free fatty acids in human bone marrow stromal cells by upregulating SIRT1.
In conclusion, the results suggest that miR-155 suppression promoted osteogenic differentiation of hBMSCs under HG-FFA conditions by targeting SIRT1. Inhibition of MiR-155 may provide a new therapeutic method for the prevention and treatment of diabetic osteoporosis. PMID: 32248286 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - April 4, 2020 Category: Physiology Authors: Qu B, He J, Zeng Z, Yang H, Liu Z, Cao Z, Yu H, Zhao W, Pan X Tags: Pflugers Arch Source Type: research

Direct monitoring of ER Ca2+ dynamics reveals that Ca2+ entry induces ER-Ca2+ release in astrocytes.
, Alonso MT Abstract Excitability in astroglia is controlled by Ca2+ fluxes from intracellular organelles, mostly from the endoplasmic reticulum (ER). Astrocytic ER possesses inositol 1,4,5-trisphosphate receptors (InsP3R) that can be activated upon stimulation through a vast number of metabotropic G-protein-coupled receptors. By contrast, the role of Ca2+-gated Ca2+ release channels is less explored in astroglia. Here we address this process by monitoring Ca2+ dynamics directly in the cytosol and the ER of astroglial cells. Cultured astrocytes exhibited spontaneous and high-K-evoked cytosolic Ca2+ transients, bot...
Source: Pflugers Archiv : European Journal of Physiology - April 3, 2020 Category: Physiology Authors: Rodríguez-Prados M, Rojo-Ruiz J, García-Sancho J, Alonso MT Tags: Pflugers Arch Source Type: research

Phosphate reabsorption in the kidney: NaPi-IIb or not IIb.
PMID: 32236864 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - April 1, 2020 Category: Physiology Authors: Burns D, Werner A Tags: Pflugers Arch Source Type: research

It takes more than two to tango: mechanosignaling of the endothelial surface.
Abstract The endothelial surface is a highly flexible signaling hub which is able to sense the hemodynamic forces of the streaming blood. The subsequent mechanosignaling is basically mediated by specific structures, like the endothelial glycocalyx building the top surface layer of endothelial cells as well as mechanosensitive ion channels within the endothelial plasma membrane. The mechanical properties of the endothelial cell surface are characterized by the dynamics of cytoskeletal proteins and play a key role in the process of signal transmission from the outside (lumen of the blood vessel) to the interior of t...
Source: Pflugers Archiv : European Journal of Physiology - April 1, 2020 Category: Physiology Authors: Fels B, Kusche-Vihrog K Tags: Pflugers Arch Source Type: research

Skeletal muscle CaV1.1 channelopathies.
Abstract CaV1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its functions as L-type calcium channel. Consequently, all known CaV1.1-related diseases are muscle diseases and the molecular and cellular disease mechanisms relate to the dual functions of CaV1.1 in this tissue. To date, four types of muscle diseases are known that can be linked to mutations in the CACNA1S gene or to splicing defects. These are hypo- and normokalemic periodic paralysis, malignant hyperthermia susceptibility, CaV1.1-related myop...
Source: Pflugers Archiv : European Journal of Physiology - March 28, 2020 Category: Physiology Authors: Flucher BE Tags: Pflugers Arch Source Type: research

Effects of syntaxins 2, 3, and 4 on rat and human epithelial sodium channel (ENaC) in Xenopus laevis oocytes.
Abstract Syntaxins are SNARE proteins and may play a role in epithelial sodium channel (ENaC) trafficking. The aim of the present study was to investigate the effects of syntaxin 2 (STX2), syntaxin 3 (STX3), and syntaxin 4 (STX4) on rat (rENaC) and human ENaC (hENaC). Co-expression of rENaC and STX3 or STX4 in Xenopus laevis oocytes increased amiloride-sensitive whole-cell currents (ΔIami) on average by 50% and 135%, respectively, compared to oocytes expressing rENaC alone. In contrast, STX2 had no significant effect on rENaC. Similar to its effect on rENaC, STX3 stimulated hENaC by 48%. In contrast, STX2 an...
Source: Pflugers Archiv : European Journal of Physiology - March 27, 2020 Category: Physiology Authors: Rauh R, Frost F, Korbmacher C Tags: Pflugers Arch Source Type: research

Calcium-induced calcium release in astroglia-a view "from the inside".
Calcium-induced calcium release in astroglia-a view "from the inside". Pflugers Arch. 2020 Mar 26;: Authors: Shmygol A PMID: 32219530 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - March 26, 2020 Category: Physiology Authors: Shmygol A Tags: Pflugers Arch Source Type: research

Irisin prevents dexamethasone-induced atrophy in C2C12 myotubes.
Abstract Irisin is a myokine secreted mainly from skeletal muscle that is known for having beneficial metabolic effects via enhancement of energy expenditure and insulin sensitivity. Studies show that irisin also acts as an autocrine/paracrine to promote myogenesis and muscle growth. However, the protective role of irisin against muscular wasting remains unclear. We confirmed that irisin secretion was upregulated by electrical pulse stimulation an in vitro exercise mimetic model. Next, we tested if irisin exerted an anti-atrophic effect on cultured C2C12 myotubes treated with dexamethasone (DEX), a representative ...
Source: Pflugers Archiv : European Journal of Physiology - March 26, 2020 Category: Physiology Authors: Chang JS, Kong ID Tags: Pflugers Arch Source Type: research

Expression of NaPi-IIb in rodent and human kidney and upregulation in a model of chronic kidney disease.
Abstract Na+-coupled phosphate cotransporters from the SLC34 and SLC20 families of solute carriers mediate transepithelial transport of inorganic phosphate (Pi). NaPi-IIa/Slc34a1, NaPi-IIc/Slc34a3, and Pit-2/Slc20a2 are all expressed at the apical membrane of renal proximal tubules and therefore contribute to renal Pi reabsorption. Unlike NaPi-IIa and NaPi-IIc, which are rather kidney-specific, NaPi-IIb/Slc34a2 is expressed in several epithelial tissues, including the intestine, lung, testis, and mammary glands. Recently, the expression of NaPi-IIb was also reported in kidneys from rats fed on high Pi. Here, we sy...
Source: Pflugers Archiv : European Journal of Physiology - March 26, 2020 Category: Physiology Authors: Motta SE, Imenez Silva PH, Daryadel A, Haykir B, Pastor-Arroyo EM, Bettoni C, Hernando N, Wagner CA Tags: Pflugers Arch Source Type: research

Neural regulation of the contractility of nutrient artery in the guinea pig tibia.
Abstract Nutrient arteries provide the endosteal blood supply to maintain bone remodelling and energy metabolism. Here, we investigated the distribution and function of perivascular nerves in regulating the contractility of the tibial nutrient artery. Changes in artery diameter were measured using a video tracking system, while the perivascular innervation was investigated using fluorescence immunohistochemistry. Nerve-evoked phasic constrictions of nutrient arteries were suppressed by phentolamine (1 μM), an α-adrenoceptor antagonist, guanethidine (10 μM), a blocker of sympathetic transmissi...
Source: Pflugers Archiv : European Journal of Physiology - March 24, 2020 Category: Physiology Authors: Fukuta H, Mitsui R, Takano H, Hashitani H Tags: Pflugers Arch Source Type: research

Peroxisome proliferator-activated receptor α (PPARα)-dependent regulation of fibroblast growth factor 23 (FGF23).
Peroxisome proliferator-activated receptor α (PPARα)-dependent regulation of fibroblast growth factor 23 (FGF23). Pflugers Arch. 2020 Mar 18;: Authors: Ewendt F, Hirche F, Feger M, Föller M Abstract Bone cells secrete fibroblast growth factor 23 (FGF23), a hormone that inhibits the synthesis of active vitamin D (1,25(OH)2D3) and induces phosphate excretion in the kidney. In addition, it exerts paracrine effects on other cells including hepatocytes, cardiomyocytes, and immune cells. The production of FGF23 is controlled by different factors including parathyroid hormone, 1,25(OH)2D3, a...
Source: Pflugers Archiv : European Journal of Physiology - March 18, 2020 Category: Physiology Authors: Ewendt F, Hirche F, Feger M, Föller M Tags: Pflugers Arch Source Type: research

Glucose transporters in the kidney in health and disease.
Abstract The kidneys filter large amounts of glucose. To prevent the loss of this valuable fuel, the tubular system of the kidney, particularly the proximal tubule, has been programmed to reabsorb all filtered glucose. The machinery involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane and the facilitative glucose transporter GLUT2 on the basolateral membrane. The proximal tubule also generates new glucose, particularly in the post-absorptive phase but also to enhance bicarbonate formation and maintain acid-base balance. The glucose reabsorbed or formed by the proximal tubule is primari...
Source: Pflugers Archiv : European Journal of Physiology - March 6, 2020 Category: Physiology Authors: Vallon V Tags: Pflugers Arch Source Type: research

Confirmation of discrepancies between exercise oximetry and American Heart Association post-exercise criteria to diagnose peripheral artery disease in patients with normal ankle-brachial index at rest.
eur A PMID: 32107634 [PubMed - as supplied by publisher] (Source: Pflugers Archiv : European Journal of Physiology)
Source: Pflugers Archiv : European Journal of Physiology - February 27, 2020 Category: Physiology Authors: Mahé G, Catillon F, Tollenaere Q, Stivalet O, Guilcher A, Le Pabic E, Jegou V, Omarjee L, Le Faucheur A Tags: Pflugers Arch Source Type: research

Pro-inflammatory cytokines in the paraventricular nucleus mediate the adipose afferent reflex in rats.
This study determined whether PICs in the PVN mediate the AAR in rats. The AAR was evaluated based on renal sympathetic nerve activity and mean arterial blood pressure in response to capsaicin injection into inguinal WAT (iWAT). PIC levels were measured by ELISA. PVN microinjection with the PICs tumor necrosis factor (TNF)-α or interleukin (IL)-1β enhanced the AAR in a dose-dependent manner. Furthermore, pretreatment via the bilateral microinjection of the TNF-α-blocker etanercept or IL-1β blocker IL-1ra into the PVN attenuated the AAR. In rats pretreated with TNF-α or IL-1β, a sub-response...
Source: Pflugers Archiv : European Journal of Physiology - February 21, 2020 Category: Physiology Authors: Lu P, Liang LW, Xu AL, Sun YY, Jiang SJ, Shi Z Tags: Pflugers Arch Source Type: research

Cardiac complex II activity is enhanced by fat and mediates greater mitochondrial oxygen consumption following hypoxic re-oxygenation.
Abstract Recent evidence suggests that mitochondrial complex II is an essential mediator of myocardial ischemia-reperfusion injury. The present study aimed to investigate the effects of fatty acid supplementation or high-fat diet (HFD) on cardiac mitochondrial activity. The changes of complex I and complex II activities and mitochondrial oxygen consumption rate (OCR) following hypoxia and re-oxygenation under these conditions were studied. Our results have shown that OCR (mitochondrial activity) was significantly increased with palmitoylcarnitine supplementation in mitochondria-enriched fraction from C57BL/6 mice ...
Source: Pflugers Archiv : European Journal of Physiology - February 20, 2020 Category: Physiology Authors: Zhu SC, Chen C, Wu YN, Ahmed M, Kitmitto A, Greenstein AS, Kim SJ, Shao YF, Zhang YH Tags: Pflugers Arch Source Type: research

Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis.
Abstract Chronic kidney disease (CKD) represents a growing public health problem associated with loss of kidney function and cardiovascular disease (CVD), the main leading cause of morbidity and mortality in CKD. It is well established that CKD is associated with gut dysbiosis. Over the past few years, there has been a growing interest in studying the composition of the gut microbiota in patients with CKD as well as the mechanisms by which gut dysbiosis contributes to CKD progression, in order to identify possible therapeutic targets to improve the morbidity and survival in CKD. The purpose of this review is to ex...
Source: Pflugers Archiv : European Journal of Physiology - February 17, 2020 Category: Physiology Authors: Rukavina Mikusic NL, Kouyoumdzian NM, Choi MR Tags: Pflugers Arch Source Type: research

Fiber-specific and whole-muscle LRP130 expression in rested, exercised, and fasted human skeletal muscle.
Abstract Leucine-rich pentatricopeptide repeat motif-containing protein (LRP130) is implicated in the control of mitochondrial gene expression and oxidative phosphorylation in the liver, partly due to its interaction with peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α). To investigate LRP130's role in healthy human skeletal muscle, we examined LRP130's fiber-type distribution and subcellular localization (n = 6), as well as LRP130's relationship with PGC-1α protein and citrate synthase (CS) maximal activity (n = 33) in vastus lateralis samples ...
Source: Pflugers Archiv : European Journal of Physiology - February 17, 2020 Category: Physiology Authors: Islam H, Ma A, Amato A, Cuillerier A, Burelle Y, Simpson CA, Quadrilatero J, Gurd BJ Tags: Pflugers Arch Source Type: research