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https://www.readbyqxmd.com/read/29463641/ultrasound-elicits-behavioral-responses-through-mechanical-effects-on-neurons-and-ion-channels-in-a-simple-nervous-system
#1
Jan Kubanek, Poojan Shukla, Alakananda Das, Stephen A Baccus, Miriam B Goodman
Focused ultrasound has been shown to stimulate excitable cells, but the biophysical mechanisms behind this phenomenon remain poorly understood. To provide additional insight, we devised a behavioralgenetic assay applied to the well-characterized nervous system of C. elegans nematodes. We found that pulsed ultrasound elicits robust reversal behavior in wild-type animals in a pressure-, duration-, and pulse protocol- dependent manner. Responses were preserved in mutants unable to sense thermal fluctuations and absent in mutants lacking neurons required for mechanosensation...
February 20, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29453757/localization-of-epithelial-sodium-channel-enac-and-cftr-in-the-germinal-epithelium-of-the-testis-sertoli-cells-and-spermatozoa
#2
Sachin Sharma, Aaron Hanukoglu, Israel Hanukoglu
Spermatogenesis starts within the seminiferous tubules of the testis by mitotic division of spermatogonia that produces spermatocytes. Meiotic division of these spermatocytes produces haploid spermatids that differentiate into spermatozoa. In this study, we examined the expression of ENaC and CFTR (a Cl - channel) in rat testicular sections using confocal microscopic immunofluorescence. The structural integrity of the seminiferous tubule sections was verified by precise phalloidin staining of the actin fibers located abundantly at both basal and adluminal tight junctions...
February 16, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29439494/listeriolysin-o-causes-enac-dysfunction-in-human-airway-epithelial-cells
#3
Guang Yang, Helena Pillich, Richard White, Istvan Czikora, Isabelle Pochic, Qiang Yue, Martina Hudel, Boris Gorshkov, Alexander Verin, Supriya Sridhar, Carlos M Isales, Douglas C Eaton, Jürg Hamacher, Trinad Chakraborty, Rudolf Lucas
Pulmonary permeability edema is characterized by reduced alveolar Na⁺ uptake capacity and capillary barrier dysfunction and is a potentially lethal complication of listeriosis. Apical Na⁺ uptake is mainly mediated by the epithelial sodium channel (ENaC) and initiates alveolar liquid clearance. Here we examine how listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes , impairs the expression and activity of ENaC. To that purpose, we studied how sub-lytic concentrations of LLO affect negative and positive regulators of ENaC expression in the H441 airway epithelial cell line...
February 11, 2018: Toxins
https://www.readbyqxmd.com/read/29432726/co-expression-of-vasoactive-intestinal-peptide-and-protein-gene-product-9-5-surrounding-the-lumen-of-human-schlemm-s-canal
#4
Pingting Ji, Liwen Chen, Jieling Gong, Yuxiang Yuan, Mu Li, Yin Zhao, Hong Zhang
Previous studies of aqueous humor outflow have focused primarily on resistance at the trabecular meshwork (TM), and little is known about the function of Schlemm's canal (SC). Here, we aimed to investigate whether SC is innervated by the peripheral nervous system. Ten eye specimens from eight donors were processed for histological analysis. CD31 was used to identify SC, after which we used protein gene product (PGP) 9.5 as a marker to detect nerve fibers around SC. We then characterized the nerves by double staining for PGP9...
February 9, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29425099/conserved-cysteines-in-the-finger-domain-of-the-epithelial-na-channel-%C3%AE-and-%C3%AE-subunits-are-proximal-to-the-dynamic-finger-thumb-domain-interface
#5
Brandon M Blobner, Xue-Ping Wang, Ossama B Kashlan
The epithelial Na+ channel (ENaC) is a member of the ENaC/Degenerin family of ion channels. In the structure of a related family member, the 'thumb' domain's base interacts with the pore, and its tip interacts with the divergent 'finger' domain. Between the base and tip, the thumb domain is characterized by a conserved 5-rung disulfide ladder holding together two anti-parallel helices. The ENaC α and γ subunits' finger domains harbor autoinhibitory tracts that can be proteolytically liberated to activate the channel, and also host an ENaC-specific pair of cysteines...
February 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29416622/mntbap-therapy-attenuates-the-downregulation-of-sodium-transporters-in-obstructive-kidney-disease
#6
Mi Liu, Yangyang Zhu, Ying Sun, Zhaoying Wen, Songming Huang, Guixia Ding, Aihua Zhang, Zhanjun Jia, Yue Zhang
Ureteral obstruction is associated with reduced expressions of renal sodium transporters, which contributes to impaired urinary concentrating capacity. In this study, we employed a synthetic mitochondrial superoxide dismutase 2 (SOD2) mimic MnTBAP to investigate the role of mitochondrial oxidative stress in modulating the sodium transporters in obstructive kidney disease. Following unilateral ureteral obstruction (UUO) for 7 days, a global reduction of sodium transporters including NHE3, NCC, NKCC2, and ENaCα was observed as determined by qRT-PCR, Western Blotting or immunohistochemistry...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29413762/the-epithelial-sodium-channel-%C3%AE-enac-is-a-downstream-therapeutic-target-of-ascl1-in-pulmonary-neuroendocrine-tumors
#7
Min He, Shanshan Liu, Sachith Gallolu Kankanamalage, Mark D Borromeo, Luc Girard, Adi F Gazdar, John D Minna, Jane E Johnson, Melanie H Cobb
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma, designated as a recalcitrant cancer by the National Cancer Institute, in urgent need of new rational therapeutic targets. Previous studies have determined that the basic helix-loop-helix transcription factor achaete-scute homolog 1 (ASCL1) is essential for the survival and progression of a fraction of pulmonary neuroendocrine cancer cells, which include both SCLC and a subset of non-SCLC. Previously, to understand how ASCL1 initiates tumorigenesis in pulmonary neuroendocrine cancer and identify the transcriptional targets of ASCL1, whole-genome RNA-sequencing analysis combined with chromatin immunoprecipitation-sequencing was performed with a series of lung cancer cell lines...
February 1, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29397423/the-phosphorylation-site-t613-in-the-%C3%AE-subunit-of-rat-epithelial-na-channel-enac-modulates-channel-inhibition-by-nedd4-2
#8
Bettina Krueger, Limin Yang, Christoph Korbmacher, Robert Rauh
The epithelial Na+ channel (ENaC) is a heteromeric channel composed of three subunits (α, β, γ). At the C-terminus of each subunit, a PY-motif allows binding of the ubiquitin ligase Nedd4-2 which plays a key role in promoting ENaC retrieval from the plasma membrane. Phosphorylation of Nedd4-2 by the serum and glucocorticoid-inducible kinase 1 (Sgk1) reduces Nedd4-2 binding to the PY-motifs. In β and γENaC, threonine residues (βT613, γT623) belong to an extracellular signal-regulated kinase (ERK) motif and directly precede the PY-motifs...
February 3, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29396543/ouabagenin-is-a-naturally-occurring-lxr-ligand-without-causing-hepatic-steatosis-as-a-side-effect
#9
Satoru Tamura, Maiko Okada, Shigeaki Kato, Yasuharu Shinoda, Norifumi Shioda, Kohji Fukunaga, Kumiko Ui-Tei, Minoru Ueda
Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies suggested that OBG has LXR-selective agonistic activity. In addition, OBG repressed the expression of epithelial sodium channel (ENaC), a LXR target gene, without causing hepatic steatosis, a typical side effect of conventional LXR ligands...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29373035/epithelial-na-channel-enac-differentially-contributes-to-shear-stress-mediated-vascular-responsiveness-in-carotid-and-mesenteric-arteries-from-mice
#10
Zoe Ashley, Sama Mugloo, Fiona J McDonald, Martin Fronius
A potential "new player" in arteries for mediating shear stress responses is the Epithelial Sodium Channel (ENaC). ENaC's contribution as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance) is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (3rd order mesenteric) arteries isolated from C57Bl/6J mice. Vessel characteristics were determined at baseline (60 mmHg, no-flow), in response to increased intraluminal pressure and shear stress using a pressure myograph...
January 26, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29371419/plasma-potassium-determines-ncc-abundance-in-adult-kidney-specific-%C3%AE-enac-knockout
#11
Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc P Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard C Rossier, Edith Hummler
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet...
January 25, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29363322/albuminuria-in-kidney-transplant-recipients-is-associated-with-increased-urinary-serine-proteases-and-activation-of-the-epithelial-sodium-channel
#12
Gitte Rye Hinrichs, Jannie Solmunde Michelsen, Rikke Zachar, Ulla Glenert Friis, Per Svenningsen, Henrik Birn, Claus Bistrup, Boye L Jensen
Albuminuria predicts adverse renal outcome in kidney transplant recipients. The present study addressed the hypothesis that albuminuria is associated with increased urine serine proteases with the ability to activate the epithelial sodium channel (ENaC) and with greater extracellular volume and higher blood pressure. In a cross-sectional design, kidney transplant recipients with (n=18) and without (n=19) albuminuria were included for office blood pressure measurements, estimation of volume status by bioimpedance, and collection of spot urine and plasma samples...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29358325/mapping-allosteric-linkage-to-channel-gating-of-extracellular-domains-in-the-human-epithelial-sodium-channel
#13
Mahmoud Shobair, Konstantin I Popov, Yan L Dang, Hong He, M Jackson Stutts, Nikolay V Dokholyan
The epithelial sodium channel (ENaC) mediates sodium absorption in lung, kidney, and colon epithelia. Channels in the ENaC/degenerin family possess an extracellular region that senses physicochemical changes in the extracellular milieu and allosterically regulates the channel opening. Proteolytic cleavage activates the ENaC opening, by the removal of specific segments in the finger domains of the α and γ ENaC subunits. Cleavage causes perturbations in the extracellular region that propagate to the channel gate...
January 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29357444/renal-potassium-handling-in-rats-with-subtotal-nephrectomy-modeling-and-analysis
#14
Anita T Layton, Aurélie Edwards, Volker Vallon
We sought to decipher the mechanisms underlying the kidney's response to changes in K+ load and intake, under physiological and pathophysiological conditions. To accomplish that goal, we applied a published computational model of epithelial transport along rat nephrons in a \Red{sham}, uninephrectomized (UNX), and 5/6-nephrectomized (5/6-NX) \Red{rats that also considers adaptations in GFR and tubular growth}. Model simulations \Red{of an acute K+ load} indicate that elevated expression levels and activities of Na+/K+-ATPase, epithelial sodium channels (ENaC), large conductance Ca2+-activated K+ channels (BK), and renal outer medullary K+ channels (ROMK), together with downregulation of sodium-chloride cotransporters (NCC), increase K+ secretion along the connecting tubule, resulting in a > 6-fold increase in urinary K+ excretion in \Red{sham rats}, which substantially exceeds the filtered K+ load...
December 13, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29357433/mccdcl1-cells-show-plasticity-consistent-with-the-ability-to-transition-between-principal-and-intercalated-cells
#15
Adrienne M Assmus, Morag K Mansley, Linda J Mullins, Audrey Peter, John J Mullins
The cortical collecting duct of the mammalian kidney plays a critical role in the regulation of body volume, sodium pH and osmolarity and is composed of two distinct cells types, principal cells and intercalated cells. Each cell type is detectable in the kidney by the localization of specific transport proteins such as Aqp2 and ENaC in principal cells and V-ATPase B1 and Cx30 in intercalated cells. mCCDcl1 cells have been widely used as a mouse principal cell line on the basis of their physiological characteristics...
December 20, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29357420/renal-na-handling-defect-associated-with-per1-dependent-non-dipping-hypertension-in-male-mice
#16
Lauren Grace Douma, Meaghan Rayann Holzworth, Kristen Solocinski, Sarah Howland Masten, Amber Holly Miller, Kit-Yan Cheng, I Jeanette Lynch, Brian D Cain, Charles S Wingo, Michelle L Gumz
Many physiological functions have a circadian rhythm, including blood pressure (BP). BP is highest during the active phase whereas during the rest period BP dips 10%-20%. Patients that do not experience this dip at night are termed "non-dippers." Non-dipping hypertension is associated with increased risk of cardiovascular disease. The mechanisms underlying non-dipping hypertension are not understood. Without the circadian clock gene Per1, C57BL/6J mice develop non-dipping hypertension on a high-salt diet plus mineralocorticoid treatment (HS/DOCP)...
January 10, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29352074/aldosterone-sgk1-and-ion-channels-in-the-kidney
#17
REVIEW
William C Valinsky, Rhian M Touyz, Alvin Shrier
Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na+, K+, and Mg2+ dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na+ (ENaC), K+ (ROMK/BK), Ca2+ (TRPV4/5/6), Mg2+ (TRPM7/6), and Cl- (ClC-K, CFTR)...
January 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29351436/therapeutic-attenuation-of-the-epithelial-sodium-channel-with-a-splunc1-derived-peptide-in-airway-diseases
#18
James F Collawn, Rafal Bartoszewski, Ahmad Lazrak, Sadis Matalon
The airway surface liquid (ASL) coats the lining of the airways and allows for efficient cilial movement and therefore effective mucociliary transport. Cell surface channels regulate the hydration status of the ASL and the two critical channels in the process are the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channel (ENaC). In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) there is loss of CFTR function or compromised CFTR function in chronic bronchitis, respectively...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29307525/veratridine-sensitive-na-channels-regulate-human-sperm-fertilization-capacity
#19
L Candenas, F M Pinto, A Cejudo-Román, C González-Ravina, M Fernández-Sánchez, N Pérez-Hernández, J Irazusta, N Subirán
AIMS: The sperm plasma membrane contains specific ion channels and transporters that initiate changes in Ca2+, Na+, K+ and H+ ions in the sperm cytoplasm. Ion channels are key regulators of the sperm membrane potential, cytoplasmic Ca2+ and intracellular pH (pHi), which leads to regulate motility, capacitation, acrosome reaction and other physiological processes crucial for successful fertilization. Expression of epithelial sodium channels (ENaC) and voltage-gated sodium channels (Nav) in human spermatozoa has been reported, but the role of Na+ fluxes sodium channels in the regulation of sperm cell function remains poorly understood...
January 4, 2018: Life Sciences
https://www.readbyqxmd.com/read/29295861/splunc1-is-an-allosteric-modulator-of-the-epithelial-sodium-channel
#20
Christine Seulki Kim, Saira Ahmad, Tongde Wu, William G Walton, Matthew R Redinbo, Robert Tarran
Cystic fibrosis (CF) is a common genetic disease with significantly increased mortality. CF airways exhibit ion transport abnormalities, including hyperactivity of the epithelial Na+ channel (ENaC). Short-palate lung and nasal epithelial clone 1 (SPLUNC1) is a multifunctional innate defense protein that is secreted into the airway lumen. We have previously demonstrated that SPLUNC1 binds to and inhibits ENaC to maintain fluid homeostasis in airway epithelia and that this process fails in CF airways. Despite this, how SPLUNC1 actually regulates ENaC is unknown...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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