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https://www.readbyqxmd.com/read/28823085/chromaffin-cells-as-a-model-to-evaluate-mechanisms-of-cell-death-and-neuroprotective-compounds
#1
REVIEW
Cristobal de Los Rios, Maria F Cano-Abad, Mercedes Villarroya, Manuela G López
In this review, we show how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action. Chromaffin cells are considered paraneurons, as they share many common features with neurons: (i) they synthesize, store, and release neurotransmitters upon stimulation and (ii) they express voltage-dependent calcium, sodium, and potassium channels, in addition to a wide variety of receptors. All these characteristics, together with the fact that primary cultures from bovine adrenal glands or chromaffin cells from the tumor pheochromocytoma cell line PC12 are easy to culture, make them an ideal model to study neurotoxic mechanisms and neuroprotective drugs...
August 19, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28822969/preconditioning-with-the-bkca-channel-activator-ns-1619-prevents-ischemia-reperfusion-induced-inflammation-and-mucosal-barrier-dysfunction-ros-and-ho-1
#2
Hongyan Dai, Meifang Wang, Parag N Patel, Theodore J Kalogeris, Yajun Liu, William Durante, Ronald J Korthuis
Activation of large conductance, calcium-activated potassium (BKCa) channels evokes cell survival programs that mitigate intestinal ischemia and reperfusion (I/R) inflammation and injury 24 hours later. The goal of the current study was to determine the role of reactive oxygen species (ROS) and heme oxygenase (HO)-1 in delayed acquisition of tolerance to I/R induced by pretreatment with the BKCa channel opener NS-1619. Superior mesentery arteries were occluded for 45 min followed by reperfusion for 70 min in wild type (WT) or HO-1 null (HO-1(-/-)) mice that were pretreated with NS-1619 or saline vehicle 24 hrs earlier...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28821664/differential-desensitization-observed-at-multiple-effectors-of-somatic-mu-opioid-receptors-underlies-sustained-agonist-mediated-inhibition-of-proopiomelanocortin-neuron-activity
#3
Philip D Fox, Shane T Hentges
Activation of somatic mu opioid receptors (MORs) in hypothalamic proopiomelanocortin (POMC) neurons leads to the activation of G-protein-coupled inward rectifier potassium (GIRK) channels and hyperpolarization, but in response to continued signaling, MORs undergo acute desensitization resulting in robust reduction in the peak GIRK current after minutes of agonist exposure. We hypothesized that the attenuation of the GIRK current would lead to a recovery of neuronal excitability whereby desensitization of the receptor would lead to a new steady-state of POMC neuron activity reflecting the sustained GIRK current observed after the initial decline from peak with continued agonist exposure...
August 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28819690/conductance-based-refractory-density-approach-comparison-with-experimental-data-and-generalization-to-lognormal-distribution-of-input-current
#4
Anton V Chizhov
The conductance-based refractory density (CBRD) approach is an efficient tool for modeling interacting neuronal populations. The model describes the firing activity of a statistical ensemble of uncoupled Hodgkin-Huxley-like neurons, each receiving individual Gaussian noise and a common time-varying deterministic input. However, the approach requires experimental validation and extension to cases of distributed input signals (or input weights) among different neurons of such an ensemble. Here the CBRD model is verified by comparing with experimental data and then generalized for a lognormal (LN) distribution of the input weights...
August 17, 2017: Biological Cybernetics
https://www.readbyqxmd.com/read/28819165/atp-sensitive-inwardly-rectifying-potassium-channel-regulation-of-viral-infections-in-honey-bees
#5
Scott T O'Neal, Daniel R Swale, Troy D Anderson
Honey bees are economically important pollinators of a wide variety of crops that have attracted the attention of both researchers and the public alike due to unusual declines in the numbers of managed colonies in some parts of the world. Viral infections are thought to be a significant factor contributing to these declines, but viruses have proven a challenging pathogen to study in a bee model and interactions between viruses and the bee antiviral immune response remain poorly understood. In the work described here, we have demonstrated the use of flock house virus (FHV) as a model system for virus infection in bees and revealed an important role for the regulation of the bee antiviral immune response by ATP-sensitive inwardly rectifying potassium (KATP) channels...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818365/the-endophytic-fungus-piriformospora-indica-enhances-arabidopsis-thaliana-growth-and-modulates-na-k-homeostasis-under-salt-stress-conditions
#6
Mohamed E Abdelaziz, Dongjin Kim, Shawkat Ali, Nina V Fedoroff, Salim Al-Babili
The mutualistic, endophytic fungus Piriformospora indica has been shown to confer biotic and abiotic stress tolerance to host plants. In this study, we investigated the impact of P. indica on the growth of Arabidopsis plants under normal and salt stress conditions. Our results demonstrate that P. indica colonization increases plant biomass, lateral roots density, and chlorophyll content under both conditions. Colonization with P. indica under salt stress was accompanied by a lower Na(+)/K(+) ratio and less pronounced accumulation of anthocyanin, compared to control plants...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28818080/standardized-systemic-phenotypic-analysis-reveals-kidney-dysfunction-as-main-alteration-of-kctd1-i27n-mutant-mice
#7
Sudhir Kumar, Birgit Rathkolb, Sibylle Sabrautzki, Stefan Krebs, Elisabeth Kemter, Lore Becker, Johannes Beckers, Raffi Bekeredjian, Robert Brommage, Julia Calzada-Wack, Lillian Garrett, Sabine M Hölter, Marion Horsch, Martin Klingenspor, Thomas Klopstock, Kristin Moreth, Frauke Neff, Jan Rozman, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabe de Angelis, Eckhard Wolf, Bernhard Aigner
BACKGROUND: Increased levels of blood plasma urea were used as phenotypic parameter for establishing novel mouse models for kidney diseases on the genetic background of C3H inbred mice in the phenotype-driven Munich ENU mouse mutagenesis project. The phenotypically dominant mutant line HST014 was established and further analyzed. METHODS: Analysis of the causative mutation as well as the standardized, systemic phenotypic analysis of the mutant line was carried out...
August 17, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28817484/levosimendan-in-acute-and-advanced-heart-failure-an-appraisal-of-the-clinical-database-and-evaluation-of-its-therapeutic-applications
#8
J Altenberger, F Gustafsson, V-P Harjola, K Karason, D Kindgen-Milles, M Kivikko, G Malfatto, Z Papp, J Parissis, P Pollesello, G Pölzl, C Tschöpe
The use of inotropes for correcting haemodynamic dysfunction in patients with congestive heart failure has been described over many decades. However, negative or insufficient data have been collected regarding the effects of cardiac glycosides, catecholamines and phosphodiesterase inhibitors on quality of life and survival. More recently, the calcium sensitizer and potassium channel-opener levosimendan has been proposed as a safer inodilator than traditional agents in some heart failure settings, such as Advanced Heart Failure...
August 15, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28815576/microrna-and-mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis-whole-mirnome-profiling-of-human-hippocampus
#9
Petra Bencurova, Jiri Baloun, Katerina Musilova, Lenka Radova, Boris Tichy, Martin Pail, Martin Zeman, Eva Brichtova, Marketa Hermanova, Sarka Pospisilova, Marek Mraz, Milan Brazdil
OBJECTIVE: Mesial temporal lobe epilepsy (mTLE) is a severe neurological disorder characterized by recurrent seizures. mTLE is frequently accompanied by neurodegeneration in the hippocampus resulting in hippocampal sclerosis (HS), the most common morphological correlate of drug resistance in mTLE patients. Incomplete knowledge of pathological changes in mTLE+HS complicates its therapy. The pathological mechanism underlying mTLE+HS may involve abnormal gene expression regulation, including posttranscriptional networks involving microRNAs (miRNAs)...
August 16, 2017: Epilepsia
https://www.readbyqxmd.com/read/28812984/modelling-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-3-in-the-human-ventricles
#10
Cunjin Luo, Kuanquan Wang, Henggui Zhang
Short QT syndrome (SQTS) is an inherited cardiac channelopathy, but at present little information is available on its pharmacological treatment. SQT3 variant (linked to the inward rectifier potassium current IK1) of SQTS, results from a gain-of-function mutation (Kir2.1 D172N) in the KCNJ2-encoded channels, which is associated with ventricular fibrillation (VF). Using biophysically-detailed human ventricular computer models, this study investigated the potential effects of quinidine, disopyramide, and E-4031 on SQT3...
August 16, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28808020/kcne1-and-kcne3-modulate-kcnq1-channels-by-affecting-different-gating-transitions
#11
Rene Barro-Soria, Rosamary Ramentol, Sara I Liin, Marta E Perez, Robert S Kass, H Peter Larsson
KCNE β-subunits assemble with and modulate the properties of voltage-gated K(+) channels. In the heart, KCNE1 associates with the α-subunit KCNQ1 to generate the slowly activating, voltage-dependent potassium current (IKs) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coassembles with KCNQ1 to form K(+) channels that are voltage-independent K(+) channels in the physiological voltage range and important for controlling water and salt secretion and absorption...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28808008/mathematical-model-reveals-role-of-nucleotide-signaling-in-airway-surface-liquid-homeostasis-and-its-dysregulation-in-cystic-fibrosis
#12
Conner I Sandefur, Richard C Boucher, Timothy C Elston
Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28805561/kcnj11-and-kcnq1-gene-polymorphisms-are-not-associated-with-post-transplant-diabetes-mellitus-in-kidney-allograft-recipients-treated-with-tacrolimus
#13
E Dabrowska-Zamojcin, M Tarnowski, M Szydlowski, M Romanowski, V Dziedziejko, K Safranow, L Domanski, A Pawlik
Post-transplant diabetes mellitus (PTDM) is a metabolic disorder occurring after solid organ transplantation during the therapy with calcineurin inhibitors. ATP-sensitive potassium channels KCNJ11 and KCNQ1 play an important role in the regulation of insulin secretion by β cells and development of diabetes mellitus. Numerous studies have confirmed the association between KCNJ11 and KCNQ1 gene polymorphisms and type 2 diabetes. The aim of this study was to examine the association between KCNJ11 and KCNQ1 gene polymorphisms and posttransplant diabetes mellitus in kidney allograft recipients treated with tacrolimus...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28804999/diversity-of-astroglial-responses-across-human-neurodegenerative-disorders-and-brain-aging
#14
Isidro Ferrer
Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease...
September 2017: Brain Pathology
https://www.readbyqxmd.com/read/28803858/in-silico-investigations-of-the-functional-impact-of-kcna5-mutations-on-atrial-mechanical-dynamics
#15
Haibo Ni, Ismail Adeniran, Henggui Zhang
A recent study has identified six novel genetic variations (D322H, E48G, A305T, D469E, Y155C, P488S) in KCNA5 (encoding Kv1.5 which carries the atrial-specific ultra-rapid delayed rectifier current, IKur) in patients with early onset of lone atrial fibrillation. These mutations are distinctive, resulting in either gain-of-function (D322H, E48G, A305T) or loss-of-function (D469E, Y155C, P488S) of IKur channels. Though affecting potassium channels, they may modulate the cellular active force and therefore atrial mechanical functions, which remains to be elucidated...
August 10, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28802123/clathrodin-hymenidin-and-oroidin-and-their-synthetic-analogues-as-inhibitors-of-the-voltage-gated-potassium-channels
#16
Nace Zidar, Aleš Žula, Tihomir Tomašič, Marc Rogers, Robert W Kirby, Jan Tytgat, Steve Peigneur, Danijel Kikelj, Janez Ilaš, Lucija Peterlin Mašič
We have prepared three alkaloids from the Agelas sponges, clathrodin, hymenidin and oroidin, and a series of their synthetic analogues, and evaluated their inhibitory effect against six isoforms of the Kv1 subfamily of voltage-gated potassium channels, Kv1.1-Kv1.6, expressed in Chinese Hamster ovary (CHO) cells using automated patch clamp electrophysiology assay. The most potent inhibitor was the (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dichloro-1H-pyrrole-2-carboxamide (6g) with IC50 values between 1...
August 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28800628/genome-wide-analysis-of-sotalol-induced-ikr-inhibition-during-ventricular-repolarization-generepol-study-lack-of-common-variants-with-large-effect-sizes
#17
Joe-Elie Salem, Marine Germain, Jean-Sébastien Hulot, Pascal Voiriot, Bruno Lebourgeois, Jean Waldura, David-Alexandre Tregouet, Beny Charbit, Christian Funck-Brentano
Many drugs used for non-cardiovascular and cardiovascular purposes, such as sotalol, have the side effect of prolonging cardiac repolarization, which can trigger life-threatening cardiac arrhythmias by inhibiting the potassium-channel IKr (KCNH2). On the electrocardiogram (ECG), IKr inhibition induces an increase in QTc and Tpeak-Tend (TpTe) interval and a decrease of T wave maximal amplitude (TAmp). These changes vary markedly between subjects, suggesting the existence of predisposing genetic factors. 990 healthy individuals, prospectively challenged with an oral 80mg sotalol dose, were monitored for changes in ventricular repolarization on ECG between baseline and 3 hours post dosing...
2017: PloS One
https://www.readbyqxmd.com/read/28794084/mechanically-induced-ectopy-via-stretch-activated-cation-nonselective-channels-is-caused-by-local-tissue-deformation-and-results-in-ventricular-fibrillation-if-triggered-on-the-repolarization-wave-edge-commotio-cordis
#18
T Alexander Quinn, Honghua Jin, Peter Lee, Peter Kohl
BACKGROUND: External chest impacts (commotio cordis) can cause mechanically induced premature ventricular excitation (PVEM) and, rarely, ventricular fibrillation (VF). Because block of stretch-sensitive ATP-inactivated potassium channels curtailed VF occurrence in a porcine model of commotio cordis, VF has been suggested to arise from abnormal repolarization caused by stretch activation of potassium channels. Alternatively, VF could result from abnormal excitation by PVEM, overlapping with normal repolarization-related electric heterogeneity...
August 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28793823/role-of-atp-sensitive-potassium-channels-in-remote-ischemic-preconditioning-induced-tissue-protection
#19
Sapna Aggarwal, Puneet Kaur Randhawa, Nirmal Singh, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) is an innovative treatment strategy that alleviates ischemia-reperfusion injury, whereby short episodes of regional ischemia and reperfusion delivered to remote organs including hind limb, kidney and intestine, and so on provide protection to the heart. The RIPC is known to reduce infarct size, serum levels of cardiac enzymes, and myocardial dysfunction in various animal species as well as in patients. There have been a large number of studies suggesting that the ATP-sensitive potassium channels (KATP channel) play a significant role as a mediator or end effector in RIPC...
September 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28793254/a-soluble-fluorescent-binding-assay-reveals-pip2-antagonism-of-trek-1-channels
#20
Cerrone Cabanos, Miao Wang, Xianlin Han, Scott B Hansen
Lipid regulation of ion channels by low-abundance signaling lipids phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA) has emerged as a central cellular mechanism for controlling ion channels and the excitability of nerves. A lack of robust assays suitable for facile detection of a lipid bound to a channel has hampered the probing of the lipid binding sites and measuring the pharmacology of putative lipid agonists for ion channels. Here, we show a fluorescent PIP2 competition assay for detergent-purified potassium channels, including TWIK-1-related K(+)-channel (TREK-1)...
August 8, 2017: Cell Reports
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