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Ion Channels

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https://www.readbyqxmd.com/read/28213824/an-approach-to-the-research-on-ion-and-water-properties-in-the-interphase-between-the-plasma-membrane-and-bulk-extracellular-solution
#1
REVIEW
Hiroshi Hibino, Madoka Takai, Hidenori Noguchi, Seishiro Sawamura, Yasufumi Takahashi, Hideki Sakai, Hitoshi Shiku
In vivo, cells are immersed in an extracellular solution that contains a variety of bioactive substances including ions and water. Classical electrophysiological analyses of epithelial cells in the stomach and small intestine have revealed that within a distance of several hundred micrometers above their apical plasma membrane, lies an extracellular layer that shows ion concentration gradients undetectable in the bulk phase. This "unstirred layer", which contains stagnant solutes, may also exist between the bulk extracellular solution and membranes of other cells in an organism and may show different properties...
February 17, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28213753/electrophysiologic-studies-on-the-risks-and-potential-mechanism-underlying-the-proarrhythmic-nature-of-azithromycin
#2
Mengdan Zhang, Ming Xie, Sha Li, Ying Gao, Shuyin Xue, Huili Huang, Kesu Chen, Fuming Liu, Long Chen
The mechanisms underlying arrhythmia induced by the clinical use of azithromycin are poorly understood. We aimed to investigate the proarrhythmic effects of azithromycin using electrocardiogram (ECG) and ion channel models. In vivo and in vitro guinea pig ECG and current and voltage clamp recordings were carried out. Azithromycin at 114.6 mg/kg (three times the clinically relevant dose) reduced heart rate (HR) and prolonged the PR, QRS and rate-corrected QT (QTc) intervals of guinea pig ECG in vivo. In vitro technique revealed that azithromycin at 207...
February 17, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28213520/cholesterol-up-regulates-neuronal-g-protein-gated-inwardly-rectifying-potassium-girk-channel-activity-in-the-hippocampus
#3
Anna N Bukiya, Serdar Durdagi, Sergei Noskov, Avia Rosenhouse-Dantsker
Hypercholesterolemia is a well-known risk factor for the development of neurodegenerative disease. However, the underlying mechanisms are mostly unknown. In recent years, it has become increasingly evident that cholesterol-driven effects on physiology and pathophysiology derive from its ability to alter the function of a variety of membrane proteins including ion channels. Yet, the effect of cholesterol on G protein-gated inwardly rectifying potassium (GIRK) channels expressed in the brain is unknown. GIRK channels mediate the actions of inhibitory brain neurotransmitters...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213505/revealing-the-concealed-nature-of-long-qt-type-3-syndrome
#4
Amara Greer-Short, Sharon A George, Steven Poelzing, Seth H Weinberg
BACKGROUND: Gain-of-function mutations in the voltage-gated sodium channel (Nav1.5) are associated with the long-QT-3 (LQT3) syndrome. Nav1.5 is densely expressed at the intercalated disk, and narrow intercellular separation can modulate cell-to-cell coupling via extracellular electric fields and depletion of local sodium ion nanodomains. Models predict that significantly decreasing intercellular cleft widths slows conduction because of reduced sodium current driving force, termed "self-attenuation...
February 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28213447/the-drosophila-postsynaptic-deg-enac-channel-ppk29-contributes-to-excitatory-neurotransmission
#5
Alexis Hill, Xingguo Zheng, Xiling Li, Ross McKinney, Dion Dickman, Yehuda Ben-Shahar
The protein family of Degenerin/Epithelial Sodium Channels (DEG/ENaC) is comprised of diverse animal-specific, non-voltage-gated ion channels that play important roles in regulating cationic gradients across epithelial barriers. Some family members are also enriched in neural tissues in both vertebrates and invertebrates. However, the specific neurophysiological functions of most DEG/ENaC-encoding genes remain poorly understood. The fruit fly Drosophila melanogaster is an excellent model for deciphering the functions of DEG/ENaC genes because its genome encodes an exceptionally large number of DEG/ENaC subunits termed pickpocket (ppk) 1-31 Here we demonstrate that ppk29 contributes specifically to the postsynaptic modulation of excitatory synaptic transmission at the larval neuromuscular junction (NMJ)...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213248/multi-reverse-flow-injection-analysis-integrated-with-multi-optical-sensor-for-simultaneous-determination-of-mn-ii-fe-ii-cu-ii-and-fe-iii-in-natural-waters
#6
Napaporn Youngvises, Kittigan Suwannasaroj, Jaroon Jakmunee, Awadh AlSuhaimi
Multi-reverse flow injection analysis (Mr-FIA) integrated with multi-optical sensor was developed and optimized for the simultaneous determination of multi ions; Mn(II), Fe(II), Cu(II) and Fe(III) in water samples. The sample/standard solutions were propelled making use of a four channels peristaltic pump whereas 4 colorimetric reagents specific for the metal ions were separately injected in sample streams using multi-syringe pump. The color zones that formed in the individual mixing coils were then streamed into multi-channels spectrometer, which comprised of four flows through cell and four pairs of light emitting diode and photodiode, whereby signals were measured concurrently...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28213106/oral-treatment-with-essential-oil-of-hyptis-spicigera-lam-lamiaceae-reduces-acute-pain-and-inflammation-in-mice-potential-interactions-with-transient-receptor-potential-trp-ion-channels
#7
Róli Rodrigues Simões, Igor Dos Santos Coelho, Stella Célio Junqueira, Glauce Regina Pigatto, Marcos José Salvador, Adair Roberto Soares Santos, Felipe Meira de Faria
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. AIM OF THE STUDY: The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. MATERIAL AND METHODS: The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28212867/protective-effect-of-spermine-against-pentylenetetrazole-kindling-epilepsy-induced-comorbidities-in-mice
#8
Mandeep Kumar, Puneet Kumar
Nitric oxide (NO), an important intracellular signaling molecule is involved in modulation of neuronal transmission. The NO level increases during epileptic activity in animal models of epilepsy. However, its role in epileptic activity remains controversial. Spermine is an endogenous polyamine; possesses anti-oxidant property and has ability to modulate ion channels and NO synthase activity. Therefore, the present study was designed to investigate the role of NO pathway in the neuroprotective effect of spermine, in Pentylenetetrazol (PTZ) induced kindling epilepsy in mice...
February 14, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28212804/potassium-channels-in-regulation-of-vascular-smooth-muscle-contraction-and-growth
#9
W F Jackson
Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca(2+) channels (VGCC), Ca(2+) influx through VGCC, intracellular Ca(2+), and VSM contraction. Membrane potential also affects release of Ca(2+) from internal stores and the Ca(2+) sensitivity of the contractile machinery such that K(+) channels participate in all aspects of regulation of VSM contraction...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212798/protein-kinase-c-as-regulator-of-vascular-smooth-muscle-function-and-potential-target-in-vascular-disorders
#10
H C Ringvold, R A Khalil
Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca(2+)-dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca(2+)-dependent α, β, and γ, novel Ca(2+)-independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212795/nanojunctions-of-the-sarcoplasmic-reticulum-deliver-site-and-function-specific-calcium-signaling-in-vascular-smooth-muscles
#11
A M Evans
Vasoactive agents may induce myocyte contraction, dilation, and the switch from a contractile to a migratory-proliferative phenotype(s), which requires changes in gene expression. These processes are directed, in part, by Ca(2+) signals, but how different Ca(2+) signals are generated to select each function is enigmatic. We have previously proposed that the strategic positioning of Ca(2+) pumps and release channels at membrane-membrane junctions of the sarcoplasmic reticulum (SR) demarcates cytoplasmic nanodomains, within which site- and function-specific Ca(2+) signals arise...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212604/high-expression-of-claudin-2-in-esophageal-carcinoma-and-precancerous-lesions-is-significantly-associated-with-the-bile-salt-receptors-vdr-and-tgr5
#12
Sohaib Abu-Farsakh, Tongtong Wu, Amy Lalonde, Jun Sun, Zhongren Zhou
BACKGROUND: Claudins are a family of integral membrane proteins and are components of tight junctions (TJs). Many TJ proteins are known to tighten the cell structure and maintain a barrier. Claudin-2 forms gated paracellular channels and allows sodium ions and other small positively charged ions to cross between adjacent cells. Recently, we found that vitamin D receptor (VDR) enhanced Claudin-2 expression in colon and that bile salt receptors VDR and Takeda G-protein coupled receptor5 (TGR5) were highly expressed in esophageal adenocarcinoma (EAC) and precancerous lesions...
February 17, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28212175/advances-in-epilepsy-gene-discovery-and-implications-for-epilepsy-diagnosis-and-treatment
#13
Joseph D Symonds, Sameer M Zuberi, Michael R Johnson
PURPOSE OF REVIEW: Epilepsy genetics is shifting from the academic pursuit of gene discovery to a clinical discipline based on molecular diagnosis and stratified medicine. We consider the latest developments in epilepsy genetics and review how gene discovery in epilepsy is influencing the clinical classification of epilepsy and informing new therapeutic approaches and drug discovery. RECENT FINDINGS: Recent studies highlighting the importance of mutation in GABA receptors, NMDA receptors, potassium channels, G-protein coupled receptors, mammalian target of rapamycin pathway and chromatin remodeling are discussed...
February 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28212111/direct-determination-of-k-q-for-farmer-type-ionization-chambers-in-a-clinical-scanned-carbon-ion-beam-using-water-calorimetry
#14
J-M Osinga-Blättermann, S Brons, S Greilich, O Jäkel, A Krauss
Until now, the dosimetry of carbon ions with ionization chambers has not reached the same level of accuracy as that of high-energy photons. This is mainly caused by the approximately threefold larger uncertainty of the k Q factor of ionization chambers, which, due to the lack of experimental data, is still derived by calculations. Measurements of absorbed dose to water, D w, by means of water calorimetry have now been performed in the entrance channel of a scanned 6 cm  ×  6 cm radiation field of 429 MeV/u carbon ions, allowing the direct calibration of ionization chambers and thus the experimental determination of k Q...
February 17, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28212021/discovery-and-development-of-1-2-bromophenyl-sulfonyl-5-methoxy-3-4-methyl-1-piperazinyl-methyl-1h-indole-dimesylate-monohydrate-suvn-502-a-novel-potent-selective-and-orally-active-serotonin-6-5-ht6-receptor-antagonist-for-potential-treatment-of-alzheimer-s
#15
Ramakrishna Nirogi, Anil Shinde, Rama Sastry Kambhampati, Abdul Rasheed Mohammed, Sangram Keshari Saraf, Rajesh Kumar Badange, Thrinath Reddy Bandyala, Venugopalarao Bhatta, Kumar Bojja, Veena Reballi, Ramkumar Subramanian, Vijay Benade, Raghava Choudary Palacharla, Gopinadh Bhyrapuneni, Pradeep Jayarajan, Vinod Goyal, Venkat Jasti
Optimization of a novel series of 3-(piperazinylmethyl) indole derivatives as 5-hydroxytryptamine-6 receptor (5-HT6R) antagonists resulted in identification of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (5al, SUVN-502) as a clinical candidate for potential treatment of cognitive disorders. It has high affinity at human 5-HT6R (Ki = 2.04 nM) and selectivity over 100 target sites which include receptors, enzymes, peptides, growth factors, ion channels, steroids, immunological factors, second messengers, and prostaglandins...
February 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28212011/a-fluorescent-anionic-mof-with-zn4-trz-2-chain-for-highly-selective-visual-sensing-of-contaminants-cr-iii-ion-and-tnp
#16
Xiao-Xia Jia, Ru-Xin Yao, Fu-Qiang Zhang, Xian-Ming Zhang
Heavy-metal ions and nitroaromatic substances are highly toxic and harmful to human health and the ecological environment. It is an urgent issue to selectively detect and capture these toxic substances. By introducing the triazole ligand to the π-conjugated aromatic carboxylate system and borrowing the organic template open framework idea, a stable fluorescent framework [Me2NH2]4[Zn6(qptc)3(trz)4]·6H2O (1) (H4qptc = terphenyl-2,5,2'5'-tetracarboxylic acid, trz = 1,2,4-triazole) has been successfully synthesized, which features Zn4(trz)2 chain-based 3D anionic structure with channels filled by [Me2NH2](+) cations...
February 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28211811/acidity-and-acid-sensing-ion-channels-in-the-normal-and-alzheimer-s-disease-brain
#17
Eric B Gonzales, Nathalie Sumien
Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28211790/flpstop-a-tool-for-conditional-gene-control-in-drosophila
#18
Yvette Erica Fisher, Helen H Yang, Jesse Isaacman-Beck, Marjorie Xie, Daryl M Gohl, Thomas R Clandinin
Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development...
February 17, 2017: ELife
https://www.readbyqxmd.com/read/28211453/mechanism-of-partial-agonism-in-ampa-type-glutamate-receptors
#19
Hector Salazar, Clarissa Eibl, Miriam Chebli, Andrew Plested
Neurotransmitters trigger synaptic currents by activating ligand-gated ion channel receptors. Whereas most neurotransmitters are efficacious agonists, molecules that activate receptors more weakly-partial agonists-also exist. Whether these partial agonists have weak activity because they stabilize less active forms, sustain active states for a lesser fraction of the time or both, remains an open question. Here we describe the crystal structure of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) ligand binding domain (LBD) tetramer in complex with the partial agonist 5-fluorowillardiine (FW)...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28209477/characterizing-the-biological-and-biochemical-profile-of-six-different-scorpion-venoms-from-the-buthidae-and-scorpionidae-family
#20
Sebastian Estrada-Gómez, Lyz Gomez-Rave, Leidy Vargas-Muñoz, Arie van der Meijden
The objective of this study was to characterize a selection of six different scorpion venoms using biological and biochemical methods, including a preliminary MS/MS and a post-translational modifications analysis. Despite the diversity of scorpion species of medical importance in Africa and Colombia, the venoms of these arachnids have been poorly studied in these two regions. We report the biochemical, electrophoretic, chromatographic profile, internal peptide sequences with a post-translational modification report, and a preliminary antitumor activity of five different scorpions of the Buthidae family, Androctonus amoreuxi, Babycurus jacksoni, Grosphus grandidieri, Hottentotta gentili and Tityus fuhrmanni, and one of the Scorpionidae family Pandinus imperator...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
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