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https://www.readbyqxmd.com/read/29677462/ondansetron-blocks-wildtype-and-p-f503l-variant-small-conductance-calcium-activated-potassium-channels
#1
Jum-Suk Ko, Shuai Guo, Jonathan Hassel, Patricia Celestino-Soper, Ty C Lynnes, James E Tisdale, James J Zheng, Stanley E Taylor, Tatiana Foroud, Michael D Murray, Richard J Kovacs, Xiaochun Li, Shien-Fong Lin, Zhenhui Chen, Matteo Vatta, Peng-Sheng Chen, Michael Rubart
The apamin-sensitive, small conductance, calcium-activated potassium (SK) current ( IKAS ) is encoded by KCNN genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT (diLQT) syndrome, we (1) screened for KCNN variants among patients with diLQT, (2) determined the properties of heterologously expressed wildtype and variant KCNN channels, and (3) determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS ...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29674316/activation-of-renal-clc-k-chloride-channels-depends-on-an-intact-n-terminus-of-their-accessory-subunit-barttin
#2
Daniel Wojciechowski, Stefan Thiemann, Christina Schaal, Alina Rahtz, Jeanne de la Roche, Birgit Begemann, Toni Becher, Martin Fischer
ClC-K channels belong to the CLC family of chloride channels and chloride/proton antiporters. They contribute to sodium chloride reabsorption in Henle's loop of the kidney and to potassium secretion into the endolymph by the stria vascularis of the inner ear. Their accessory subunit barttin stabilizes the ClC-K/barttin complex, promotes its insertion into the surface membrane, and turns the pore-forming subunits into a conductive state. Barttin mutations cause Bartter syndrome type IV, a salt wasting nephropathy with sensorineural deafness...
April 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29673714/discovery-and-evaluation-of-nna-v-1-5-sodium-channel-blockers-with-potent-cell-invasion-inhibitory-activity-in-breast-cancer-cells
#3
Shilpa Dutta, Osbaldo Lopez Charcas, Samuel Tanner, Frédéric Gradek, Virginie Driffort, Sébastien Roger, Katri Selander, Sadanandan E Velu, Wayne Brouillette
Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and the important roles that they play in excitable cells. Recently, their presence has been recognized in non-excitable cells such as cancer cells and their overexpression has been shown to be associated with metastatic behavior in a variety of human cancers. The neonatal isoform of the VGSC subtype, Nav 1.5 (nNav 1.5) is overexpressed in the highly aggressive human breast cancer cell line, MDA-MB-231...
April 3, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29672308/modulation-of-pacemaker-potentials-in-murine-small-intestinal-interstitial-cells-of-cajal-by-gamisoyo-san-a-traditional-chinese-herbal-medicine
#4
Doeun Kim, Jung Nam Kim, Joo Hyun Nam, Jong Rok Lee, Sang Chan Kim, Byung Joo Kim
BACKGROUND: The Gamisoyo-san (GSS) has been used for -improving the gastrointestinal (GI) symptoms. The purpose of this study was to investigate the effects of GSS, a traditional Chinese herbal medicine, on the pacemaker potentials of mouse small intestinal interstitial cells of Cajal (ICCs). METHODS: ICCs from the small intestines were dissociated and cultured. Whole-cell patch-clamp configuration was used to record pacemaker potentials and membrane currents. RESULTS: GSS depolarized ICC pacemaker potentials in a dose-dependent manner...
April 19, 2018: Digestion
https://www.readbyqxmd.com/read/29671361/liposomal-quercetin-potentiates-maxi-k-channel-openings-in-smooth-muscles-and-restores-its-activity-after-oxidative-stress
#5
Mariia I Melnyk, Dariia O Dryn, Lina T Al Kury, Alexander V Zholos, Anatoly I Soloviev
The effects of quercetin-loaded liposomes (PCL-Q) and their constituents, that is, free quercetin (Q) and 'empty' phosphatidylcholine vesicles (PCL), on maxi-K channel activity were studied in single mouse ileal myocytes before and after H2 O2 -induced oxidative stress. Macroscopic Maxi-K channel currents were recorded using whole-cell patch clamp techniques, while single BKCa channel currents were recorded in the cell-attached configuration. Bath application of PCL-Q (100 μg/ml of lipid and 3 μg/ml of quercetin) increased single Maxi-K channel activity more than threefold, from 0...
April 19, 2018: Journal of Liposome Research
https://www.readbyqxmd.com/read/29671217/cyproheptadine-regulates-pyramidal-neuron-excitability-in-mouse-medial-prefrontal-cortex
#6
Yan-Lin He, Kai Wang, Qian-Ru Zhao, Yan-Ai Mei
Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K+ current (IK ) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current...
April 18, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29669164/galantamine-is-not-a-positive-allosteric-modulator-of-human-%C3%AE-4%C3%AE-2-or-%C3%AE-7-nicotinic-acetylcholine-receptors
#7
Natalia M Kowal, Philip K Ahring, Vivian W Y Liao, Dinesh C Indurti, Benjamin S Harvey, Susan M O'Connor, Mary Chebib, Elin S Olafsdottir, Thomas Balle
BACKGROUND AND PURPOSE: The alkaloid galantamine was originally isolated from the green snowdrop Galanthus woronowii and is currently marketed as a drug for treatment of mild to moderate dementia in Alzheimer's disease patients. In addition to a well-documented proficiency of inhibiting the acetylcholinesterase enzyme, galantamine has been reported to increase neuronal nicotinic acetylcholine (nACh) receptor function by acting as a positive allosteric modulator. Yet, there remains controversy regarding these findings in the literature...
April 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29668881/hyperactive-ryanodine-receptors-in-human-heart-failure-and-ischemic-cardiomyopathy-reside-outside-of-couplons
#8
Eef Dries, Demetrio J Santiago, Guillaume Gilbert, Ilse Lenaerts, Bert Vandenberk, Chandan K Nagaraju, Daniel M Johnson, Patricia Holemans, H Llewelyn Roderick, Niall Macquaide, Piet Claus, Karin R Sipido
Aims: In ventricular myocytes from humans and large mammals, the transverse and axial tubular system (TATS) network is less extensive than in rodents with consequently a greater proportion of ryanodine receptors (RyRs) not coupled to this membrane system. TATS remodeling in heart failure (HF) and after myocardial infarction (MI) increases the fraction of non-coupled RyR. Here we investigate whether this remodeling alters the activity of coupled and non-coupled RyR sub-populations through changes in local signaling...
April 14, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29665767/nano-cuo-impairs-spatial-cognition-associated-with-inhibiting-hippocampal-ltp-via-affecting-glutamatergic-neurotransmission-in-rats
#9
Xiaoliang Li, Wei Sun, Lei An
Manufactured metal nanoparticles and their applications are continuously expanding because of their unique characteristics while their increasing use may predispose to potential health problems. Several studies have reported the adverse effects of copper oxide nanoparticles (nano-CuO) relative to ecotoxicity and cell toxicity, whereas little is known about the neurotoxicity of nano-CuO. The present study aimed to examine its effects on spatial cognition, hippocampal function, and the possible mechanisms. Male Wistar rats were used to establish an animal model, and nano-CuO was administered at a dose of 0...
January 1, 2018: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/29665277/the-expression-of-endogenous-voltage-gated-potassium-channels-in-hek293-cells-is-affected-by-culture-conditions
#10
Arturo Ponce, Aida Castillo, Lorena Hinojosa, Jacqueline Martinez-Rendon, Marcelino Cereijido
HEK293 cells are widely used as a host for expression of heterologous proteins; yet, little care has been taken to characterize their endogenous membrane components, including ion channels. In this work, we aimed to describe the biophysical and pharmacological properties of endogenous, voltage-dependent potassium currents (IKv). We also examined how its expression depends on culture conditions. We used the electrophysiological technique of whole-cell patch clamp to record ion currents from HEK293 cells. We found that HEK cells express endogenous, voltage-dependent potassium currents...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29663284/fluoxetine-modulates-the-activity-of-hypothalamic-pomc-neurons-via-mtor-signaling
#11
Ilaria Barone, Riccardo Melani, Marco Mainardi, Gaia Scabia, Manuela Scali, Alessia Dattilo, Giovanni Ceccarini, Paolo Vitti, Ferruccio Santini, Lamberto Maffei, Tommaso Pizzorusso, Margherita Maffei
Hypothalamic proopiomelanocortin (POMC) neurons are important players in the regulation of energy homeostasis; we previously demonstrated that environmental stimulation excites arcuate nucleus circuits to undergo plastic remodeling, leading to altered ratio between excitatory and inhibitory synaptic contacts on these neurons. The widely used selective serotonin reuptake inhibitor fluoxetine (FLX) is known to affect body weight. On the other hand, FLX administration mimics the effects of environmental stimulation on synaptic plasticity in the hippocampus and cortex...
April 16, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29662441/characterization-of-hair-cell-like-cells-converted-from-supporting-cells-after-notch-inhibition-in-cultures-of-the-organ-of-corti-from-neonatal-gerbils
#12
Yi Li, Shuping Jia, Huizhan Liu, Tomoko Tateya, Weiwei Guo, Shiming Yang, Kirk W Beisel, David Z Z He
The senses of hearing and balance depend upon hair cells, the sensory receptors of the inner ear. Hair cells transduce mechanical stimuli into electrical activity. Loss of hair cells as a result of aging or exposure to noise and ototoxic drugs is the major cause of noncongenital hearing and balance deficits. In the ear of non-mammals, lost hair cells can spontaneously be replaced by production of new hair cells from conversion of supporting cells. Although supporting cells in adult mammals have lost that capability, neonatal supporting cells are able to convert to hair cells after inhibition of Notch signaling...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29659843/a-computed-tomography-based-planning-tool-for-predicting-difficulty-of-minimally-invasive-aortic-valve-replacement
#13
Mustafa A Elattar, Abdullah Kaya, Nils R Planken, Jan Baan, Ed T Vanbavel, Bas A J M de Mol, Henk A Marquering
OBJECTIVES: Minimally invasive aortic valve replacement has proven its value over the last decade by its significant advancement and reduction in mortality, morbidity and admission time. However, minimally invasive aortic valve replacement is associated with some on-site difficulties such as limited aortic annulus exposure. Currently, computed tomography scans are used to evaluate the anatomical relationship among the intercostal spaces, ascending aorta and aortic valve prior to surgery...
April 12, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29656606/a-meta-analysis-on-the-surgical-management-of-paraganglioma-of-the-carotid-body-per-shamblin-class
#14
Thijs T G Jansen, Henri A M Marres, Johannes H A M Kaanders, Henricus P M Kunst
OBJECTIVE: The aim of the current study is to evaluate the risk associated with different types of surgery for carotid body paraganglioma of different Shamblin class. A meta-analysis was conducted to evaluate per tumour class, the local control, cranial nerve damage and complication rates of different techniques using internal carotid artery (ICA) and external carotid artery (ECA) ligation, clamping or bypassing, as well as the cranio-caudal versus caudo-cranial techniques. DESIGN: A meta-analysis is conducted after a systematic search in PubMed and the Cochrane library, in accordance with the PRISMA guidelines...
April 15, 2018: Clinical Otolaryngology
https://www.readbyqxmd.com/read/29650545/regulation-of-blood-pressure-by-targeting-ca-v-1-2-galectin-1-protein-interaction
#15
Zhenyu Hu, Guang Li, Jiong-Wei Wang, Suet Yen Chong, Dejie Yu, Xiaoyuan Wang, Jia Lin Soon, Mui Cheng Liang, Yuk Peng Wong, Na Huang, Henry M Colecraft, Ping Liao, Tuck Wah Soong
Background -L-type CaV 1.2 channels play crucial roles in regulation of blood pressure. Galectin-1 (Gal-1), has been reported to bind to the I-II loop of CaV 1.2 channels to reduce their current density. However, the mechanistic understanding for the down-regulation of CaV 1.2 channels by Gal-1, and whether Gal-1 plays a direct role in blood pressure regulation remain unclear. Methods - In vitro experiments involving co-IP, western blot, patch-clamp recordings, immunohistochemistry and pressure myography were used to evaluate the molecular mechanisms by which Gal-1 down-regulates CaV 1...
April 12, 2018: Circulation
https://www.readbyqxmd.com/read/29649954/anatomical-considerations-and-open-surgery-to-treat-juxtarenal-abdominal-aortic-aneurysms
#16
Georgiana Samoila, Ian Michael Williams
INTRODUCTION: Historically, the open approach to the abdominal aorta has been transperitoneal (TP). In comparison, a retroperitoneal (RP) incision exposes the lateral wall of the suprarenal aorta for clamp application and midline structures such as the duodenum and pancreas are not encountered. Proximal clamp position for open repair of juxtarenal abdominal aortic aneurysm (JR-AAA) is suprarenal, supra-superior mesenteric, or supraceliac. While RP and TP approaches have previously been compared for physiological reasons, there are currently no randomized controlled trials comparing these methods from an anatomical perspective...
January 1, 2018: Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/29643800/interaction-of-norepinephrine-and-glucocorticoids-modulate-inhibition-of-principle-cells-of-layer-ii-medial-entorhinal-cortex-in-male-mice
#17
Jeremiah P Hartner, Laura A Schrader
Spatial memory processing requires functional interaction between the hippocampus and the medial entorhinal cortex (MEC). The grid cells of the MEC are most abundant in layer II and rely on a complex network of local inhibitory interneurons to generate spatial firing properties. Stress can cause spatial memory deficits in males, but the specific underlying mechanisms affecting the known memory pathways remain unclear. Stress activates both the autonomic nervous system and the hypothalamic-pituitary-adrenal axis to release norepinephrine (NE) and glucocorticoids, respectively...
2018: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29643381/pannexin-1-sustains-the-electrophysiological-responsiveness-of-retinal-ganglion-cells
#18
Galina Dvoriantchikova, Alexey Pronin, Sarah Kurtenbach, Abduqodir Toychiev, Tsung-Han Chou, Christopher W Yee, Breanne Prindeville, Junior Tayou, Vittorio Porciatti, Botir T Sagdullaev, Vladlen Z Slepak, Valery I Shestopalov
Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29643254/new-targets-for-old-drugs-cardiac-glycosides-inhibit-atrial-specific-k2p3-1-task-1-channels
#19
Constanze Schmidt, Felix Wiedmann, Anne-Rike Gaubatz, Antonius Ratte, Hugo A Katus, Dierk Thomas
Cardiac glycosides have been used in the treatment of arrhythmias for more than 200 years. Two-pore-domain (K2P) potassium channels regulate cardiac action potential repolarization. Recently, K2P3.1 (TASK-1) has been implicated in atrial fibrillation (AF) pathophysiology and was suggested as atrial-selective antiarrhythmic drug target. We hypothesized that blockade of cardiac K2P channels contributes to the mechanism of action of digitoxin and digoxin. All functional human K2P channels were screened for interactions with cardiac glycosides...
April 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29642561/%C3%AE-nicotinamide-adenine-dinucleotide-%C3%AE-nad-inhibits-atp-dependent-il-1%C3%AE-release-from-human-monocytic-cells
#20
Sebastian Daniel Hiller, Sarah Heldmann, Katrin Richter, Innokentij Jurastow, Mira Küllmar, Andreas Hecker, Sigrid Wilker, Gabriele Fuchs-Moll, Ivan Manzini, Günther Schmalzing, Wolfgang Kummer, Winfried Padberg, J Michael McIntosh, Jelena Damm, Anna Zakrzewicz, Veronika Grau
While interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1β maturation, is released from damaged cells along with β-nicotinamide adenine dinucleotide (β-NAD). Here, we tested the hypothesis that β-NAD controls ATP-signaling and, hence, IL-1β release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2'(3')- O -(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of β-NAD...
April 10, 2018: International Journal of Molecular Sciences
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