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https://www.readbyqxmd.com/read/29782492/molecular-basis-of-inhibition-of-acid-sensing-ion-channel-1a-by-diminazene
#1
Aram J Krauson, James G Rooney, Marcelo D Carattino
Acid-sensing ion channels (ASICs) are trimeric proton-gated cation permeable ion channels expressed primarily in neurons. Here we employed site-directed mutagenesis and electrophysiology to investigate the mechanism of inhibition of ASIC1a by diminazene. This compound inhibits mouse ASIC1a with a half-maximal inhibitory concentration (IC50) of 2.4 μM. At first, we examined whether neutralizing mutations of Glu79 and Glu416 alter diminazene block. These residues form a hexagonal array in the lower palm domain that was previously shown to contribute to pore opening in response to extracellular acidification...
2018: PloS One
https://www.readbyqxmd.com/read/29781252/subtype-selective-inhibition-of-acid-sensing-ion-channel-3-by-a-natural-flavonoid
#2
Xiao-Gang Yan, Wei-Guang Li, Xin Qi, Jia-Jie Zhu, Chen Huang, Shao-Ling Han, Qin Jiang, Tian-Le Xu, Jian-Hua Liu
AIMS: Acid-sensing ion channels (ASICs) are extracellular proton-gated cation channels that have been implicated in multiple physiological and pathological processes, and peripheral ASIC3 prominently participate into the pathogenesis of chronic pain, itch, and neuroinflammation, which necessitates the need for discovery and development of novel modulators in a subtype-specific manner. METHODS: Whole-cell patch clamp recordings and behavioral assays were used to examine the effect of several natural compounds on the ASIC-mediated currents and acid-induced nocifensive behavior, respectively...
May 20, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29767545/pharmacogenetics-of-novel-oral-anticoagulants-a-review-of-identified-gene-variants-future-perspectives
#3
Adna Ašić, Damir Marjanović, Jure Mirat, Dragan Primorac
Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected...
May 16, 2018: Personalized Medicine
https://www.readbyqxmd.com/read/29763692/pharmacological-evidence-that-dapi-inhibits-nhe2-in-fundulus-heteroclitus-acclimated-to-freshwater
#4
Kevin V Brix, Colin J Brauner, Dolph Schluter, Chris M Wood
Ionoregulation in the euryhaline killifish Fundulus heteroclitus has been intensively studied over the last two decades using a variety of techniques. However, there has been limited use of pharmacological inhibitors to identify proteins involved in ion transport for this species. In this study, we used a range of pharmacological inhibitors (EIPA, DAPI, ethoxzolamide, bumetanide, bafilomycin, phenamil, hydrochlorothiazide) to investigate the proteins involved in Na+ transport in freshwater (1 mM Na+ ) acclimated F...
May 12, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29739981/dual-actions-of-psalmotoxin-at-asic1a-and-asic2a-heteromeric-channels-asic1a-2a
#5
Yi Liu, Rebecca Hagan, Jeffrey Schoellerman
Acid-Sensing Ion Channels (ASICs) are gated by extracellular protons and play important roles in physiological and pathological states, such as pain and stroke. ASIC1a and ASIC2a, two of the most highly expressed subunits in the brain, form functional homo- and hetero-meric (ASIC1a/2a) channels. The function of ASIC1a has been widely studied using psalmotoxin (PcTx1), a venom-derived peptide, as an ASIC1a-selective antagonist. Here, using whole-cell patch clamp, we show that PcTx1 has dual actions at ASIC1a/2a...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739425/naked-mole-rat-cortical-neurons-are-resistant-to-acid-induced-cell-death
#6
Zoé Husson, Ewan St John Smith
Regulation of brain pH is a critical homeostatic process and changes in brain pH modulate various ion channels and receptors and thus neuronal excitability. Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various proteins and ion channels, among which acid-sensing ion channels (ASICs) a family of primarily Na+ permeable ion channels, which alongside classical excitotoxicity causes neuronal death. Naked mole-rats (NMRs, Heterocephalus glaber) are long-lived, fossorial, eusocial rodents that display remarkable behavioral/cellular hypoxia and hypercapnia resistance...
May 9, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29736613/inhibition-of-acid-sensing-ion-channel-3-aggravates-seizures-by-regulating-nmdar-function
#7
Qian Cao, Zhe-Man Xiao, Xi Wang, Chao Weng, Man Ding, Fan Zhu, Zu-Neng Lu
The existing data about whether acid sensing ion channels (ASICs) are proconvulsant or anticonvulsant are controversial. Particularly, acid sensing ion channel 3 (ASIC3) is the most sensitive to extracellular pH and has the characteristic ability to generate a biphasic current, but few studies have focused on the role of ASIC3 in seizure. Here we found ASIC3 expression was increased in the hippocampus of pilocarpine induced seizure rats, as well as in hippocampal neuronal cultures undergoing epileptiform discharge elicited by Mg2+ -free media...
May 7, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29733285/a-column-row-parallel-ultrasound-imaging-architecture-for-3-d-plane-wave-imaging-and-tx-second-order-harmonic-distortion-reduction
#8
Kailiang Chen, Byung Chul Lee, Kai E Thomenius, Butrus T Khuri-Yakub, Hae-Seung Lee, Charles G Sodini
We propose a column-row-parallel imaging front-end architecture for integrated and low-power 3-D medical ultrasound imaging. The column-row-parallel architecture offers linear-scaling interconnection, acquisition, and programming time with row-by-row or column-by-column operations, while supporting volumetric imaging functionality and fault-tolerance against possible transducer element defects with per-element controls. The combination of column-parallel selection logic, row-parallel selection logic, and per-element selection logic reaches a balance between flexible imaging aperture definition and manageable imaging data/control interface to a 2-D array...
May 2018: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/29684594/new-apetx-like-peptides-from-sea-anemone-heteractis-crispa-modulate-asic1a-channels
#9
Rimma Kalina, Irina Gladkikh, Pavel Dmitrenok, Oleg Chernikov, Sergey Koshelev, Aleksandra Kvetkina, Sergey Kozlov, Emma Kozlovskaya, Margarita Monastyrnaya
Sea anemones are an abundant source of various biologically active peptides. The hydrophobic 20% ethanol fraction of tropical sea anemone Heteractis crispa was shown to contain at least 159 peptide compounds including neurotoxins, proteinase and α-amylase inhibitors, as well as modulators of acid-sensing ion channels (ASICs). The three new peptides, π-AnmTX Hcr 1b-2, -3, and -4 (41 aa) (short names Hcr 1b-2, -3, -4), identified by a combination of reversed-phase liquid chromatography and mass spectrometry were found to belong to the class 1b sea anemone neurotoxins...
April 22, 2018: Peptides
https://www.readbyqxmd.com/read/29655911/antinociceptive-activity-of-riparin-ii-from-aniba-riparia-further-elucidation-of-the-possible-mechanisms
#10
Alyne Mara Rodrigues de Carvalho, Leonardo Freire Vasconcelos, Nayrton Flávio Moura Rocha, Emiliano Ricardo Vasconcelos Rios, Marília Leite Dias, Marta Maria de França Fonteles, Danielle Macêdo Gaspar, José Maria Barbosa Filho, Stanley Juan Chavez Gutierrez, Francisca Cléa Florenço de Sousa
Riparin II (RipII) has an anti-inflammatory activity potentially due its ability to decrease TNF-α and IL-1β production and its histamine antagonism. The objective of this study was to evaluate the role of RipII in the pain process and the possible antinociceptive mechanisms involved, using classic models of nociception. Male Swiss mice were used in the assays. Determinate the acute toxicity according to the OECD 425 test guideline. The models used were the acetic acid-, formalin-, hot plate and glutamate-induced nociception...
April 12, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29642506/fpga-based-adaptive-rate-and-manifold-pattern-projection-for-structured-light-3d-camera-system
#11
Muhammad Atif, Sukhan Lee
The quality of the captured point cloud and the scanning speed of a structured light 3D camera system depend upon their capability of handling the object surface of a large reflectance variation in the trade-off of the required number of patterns to be projected. In this paper, we propose and implement a flexible embedded framework that is capable of triggering the camera single or multiple times for capturing single or multiple projections within a single camera exposure setting. This allows the 3D camera system to synchronize the camera and projector even for miss-matched frame rates such that the system is capable of projecting different types of patterns for different scan speed applications...
April 8, 2018: Sensors
https://www.readbyqxmd.com/read/29627444/inhalational-anesthetics-accelerate-desensitization-of-acid-sensing-ion-channels
#12
Linda Lehmke, Mark Coburn, Manfred Möller, Rosmarie Blaumeiser-Debarry, Pia Lenzig, Dominik Wiemuth, Stefan Gründer
Acid-sensing ion channels (ASICs) are neuronal Na+ channels that are activated by extracellular acidification. Inhibiting ASICs is neuroprotective in mouse models of ischemic stroke. As inhalational anesthetics interact with many ion channels and as some of them have neuroprotective effects, we hypothesized that inhalational anesthetics modulate ASICs. We expressed different homo- and heteromeric ASICs heterologously in Xenopus oocytes. We co-applied with acidic pH the halogenated inhalational anesthetics sevoflurane, desflurane, and isoflurane and the noble gases xenon and argon at concentrations that are roughly equivalent to their minimal alveolar concentrations and analyzed their effect on current kinetics and amplitude...
April 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29617678/increased-asics-expression-via-the-camkii-creb-pathway-in-a-novel-mouse-model-of-trigeminal-pain
#13
Yan Wang, Xiujuan Fu, Lifang Huang, Xi Wang, Zuneng Lu, Fan Zhu, Zheman Xiao
BACKGROUND/AIMS: Migraine is a disabling condition that severely impacts socioeconomic function and quality of life. The focus of this study was to develop a mouse model of trigeminal pain that mimics migraine. METHODS: After undergoing dural cannulation surgery, mice were treated with repeated dural doses of an acidic solution to induce trigeminal pain. RESULTS: The method elicited intermittent, head-directed wiping and scratching as well as the expression of both the c-FOS gene in the spinal trigeminal nucleus caudalis and calcitonin gene related peptide (CGRP) in the periaqueductal grey matter...
March 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29595330/neuroprotective-effects-of-psalmotoxin-1-an-acid-sensing-ion-channel-asic-inhibitor-in-ischemia-reperfusion-in-mouse-eyes
#14
Adnan Dibas, Cameron Millar, Abraham Al-Farra, Thomas Yorio
PURPOSE: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs) after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of ASIC1a provides RGC neuroprotection. METHODS: Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. RGC function was measured by Pattern electroretinography (PERG)...
March 29, 2018: Current Eye Research
https://www.readbyqxmd.com/read/29584803/involvement-of-acid-sensing-ion-channel-1a-in-gastric-carcinoma-cell-migration-and-invasion
#15
Xin Chen, Xue Sun, Zhe Wang, Xiaojun Zhou, Lu Xu, Feng'e Li, Xingding Zhang, Ji'an Pan, Lin Qi, Haixin Qian, Zhongqi Mao
Acidic microenvironment, particularly acid-sensing ion channel 1a (ASIC1a), has been reported to promote carcinoma cell proliferation as well as migration. In this study, we explored the effect of ASIC1a on migration and invasion of gastric carcinoma (GC). ASIC1a expression levels were examined in paired GC and adjacent normal tissues from 16 patients by immunohistochemistry. Reverse transcription real-time PCR and immunoblotting were conducted to assess the ASIC1a expression levels in the GC cell line AGS after transfection with ASIC1a small hairpin RNA (shRNA)...
March 23, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29574226/role-of-asic1a-in-a%C3%AE-induced-synaptic-alterations-in-the-hippocampus
#16
D Mango, R Nisticò
Acid-sensing ion channels (ASICs) are widely expressed in the mammalian central nervous system where they play a key role in synaptic transmission and in specific forms of memory. On the other hand, ASICs can be persistently active under pathological conditions contributing to neuronal damage in ischemic stroke, brain trauma, epilepsy and Parkinson's disease. However, to date no experimental evidence has linked ASICs to Alzheimer's disease (AD). Aim of the present work was to investigate, in CA1 pyramidal neurons, the possible involvement of ASIC1a in the Aβ-mediated effect on metabotropic glutamate (mGlu) receptor dependent transmission...
March 21, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29566331/heteroarylguanidines-as-allosteric-modulators-of-asic1a-and-asic3-channels
#17
Omar Alijevic, Hassan Hammoud, Anand Vaithia, Viktor Trendafilov, Maud Bollenbach, Martine Schmitt, Frederic Bihel, Stephan Kellenberger
Acid-sensing ion channels (ASICs) are neuronal Na+ -selective ion channels that open in response to a rapid extracellular acidification. They are involved in pain, fear, learning and neurodegeneration after ischemic stroke. 2-Guanidine-4-methylquinazoline (GMQ) was recently discovered as the first nonproton activator of ASIC3. GMQ is of interest as a gating modifier and pore blocker of ASICs. It has however a low potency, and exerts opposite effects on ASIC1a and ASIC3. To further explore the molecular mechanisms of GMQ action, we have used the guanidinium moiety of GMQ as a scaffold and tested the effects of different GMQ derivatives on the ASIC pH dependence and maximal current...
March 22, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29561183/asic3-fine-tunes-bladder-sensory-signaling
#18
Nicola Montalbetti, James G Rooney, Allison L Marciszyn, Marcelo D Carattino
Acid-sensing ion channels (ASICs) are trimeric proton-activated cation selective neuronal channels that are considered to play important roles in mechanosensation and nociception. Here we investigated the role of ASIC3, a subunit primarily expressed in sensory neurons, in bladder sensory signaling and function. We found that extracellular acidification evokes a transient increase in current, consistent with the kinetics of activation and desensitization of ASICs, in ~ 25% of the bladder sensory neurons harvested from both wild type (WT) and ASIC3 knockout (KO) mice...
March 21, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29555470/acute-stress-enhances-learning-and-memory-by-activating-acid-sensing-ion-channels-in-rats
#19
Shunjie Ye, Rong Yang, Qiuju Xiong, Youhua Yang, Lianying Zhou, Yeli Gong, Changlei Li, Zhenhan Ding, Guohai Ye, Zhe Xiong
Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs...
April 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29549622/targeted-acid-sensing-ion-channel-therapies-for-migraine
#20
REVIEW
Nazia Karsan, Eric B Gonzales, Gregory Dussor
Acid-sensing ion channels (ASICs) are a family of ion channels, consisting of four members; ASIC1 to 4. These channels are sensitive to changes in pH and are expressed throughout the central and peripheral nervous systems-including brain, spinal cord, and sensory ganglia. They have been implicated in a number of neurological conditions such as stroke and cerebral ischemia, traumatic brain injury, and epilepsy, and more recently in migraine. Their expression within areas of interest in the brain in migraine, such as the hypothalamus and PAG, their demonstrated involvement in preclinical models of meningeal afferent signaling, and their role in cortical spreading depression (the electrophysiological correlate of migraine aura), has enhanced research interest into these channels as potential therapeutic targets in migraine...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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