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https://www.readbyqxmd.com/read/29156592/activation-of-trek-1-but-not-trek-2-channel-by-mood-stabilizers
#1
Eun-Jin Kim, Dong Kun Lee, Seong-Geun Hong, Jaehee Han, Dawon Kang
Earlier studies have demonstrated that the tandem pore domain weak inward rectifying K⁺ channel (TWIK)-related K⁺ (TREK)-1 channel is inhibited by antidepressants and is associated with major depression. However, little is known about the effect of mood stabilizers that are commonly used for treatment of bipolar disorder on TREK channels, members of the two-pore domain K⁺ (K2P) channel family. This study sought to investigate the effect of mood stabilizers on TREK-1 and TREK-2 channels. HEK-293A cells were transfected with human TREK-1 or TREK-2 DNA...
November 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29154951/regulation-of-neural-ion-channels-by-muscarinic-receptors
#2
REVIEW
David A Brown
The excitable behaviour of neurons is determined by the activity of their endogenous membrane ion channels. Since muscarinic receptors are not themselves ion channels, the acute effects of muscarinic receptor stimulation on neuronal function are governed by the effects of the receptors on these endogenous neuronal ion channels. This review considers some principles and factors determining the interaction between subtypes and classes of muscarinic receptors with neuronal ion channels, and summarizes the effects of muscarinic receptor stimulation on a number of different channels, the mechanisms of receptor - channel transduction and their direct consequences for neuronal activity...
November 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29143559/k-cl-co-transporter-2-kcc2-a-membrane-trafficking-perspective
#3
Bor Luen Tang
K(+)-Cl(-) co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl(-) levels. It also has an ion transporter-independent structural role in modulating the maturation and regulation of excitatory glutamatergic synapses. KCC2 levels are developmentally regulated, and a postnatal upregulation of KCC2 generates a low intracellular chloride concentration that allows the neurotransmitters γ-aminobutyric acid (GABA) and glycine to exert inhibitory neurotransmission through its Cl(-) permeating channel...
November 16, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29093568/experimental-preeclampsia-in-rats-affects-vascular-gene-expression-patterns
#4
Simone V Lip, Anne Marijn van der Graaf, Marjon J Wiegman, Sicco A Scherjon, Mark V Boekschoten, Torsten Plösch, Marijke M Faas
Normal pregnancy requires adaptations of the maternal vasculature. During preeclampsia these adaptations are not well established, which may be related to maternal hypertension and proteinuria. The effects of preeclampsia on the maternal vasculature are not yet fully understood. We aimed to evaluate gene expression in aortas of pregnant rats with experimental preeclampsia using a genome wide microarray. Aortas were isolated from pregnant Wistar outbred rats with low-dose LPS-induced preeclampsia (ExpPE), healthy pregnant (Pr), non-pregnant and low-dose LPS-infused non-pregnant rats...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29091893/isoflurane-post-conditioning-down-regulates-expression-of-aquaporin-4-in-rats-with-cerebral-ischemia-reperfusion-injury-and-is-possibly-related-to-bone-morphogenetic-protein-4-smad1-5-8-signaling-pathway
#5
Min Yuan, Mingyue Ge, Jiangwen Yin, Zhigang Dai, Liping Xie, Yan Li, Xuejiao Liu, Li Peng, Guixing Zhang, Junqiang Si, Ketao Ma, Sheng Wang
AIM: Aquaporins (AQPs) are water-channels that play important roles in brain water homeostasis and cerebral edema induced by brain injury. This study aimed to investigate the relationship between AQP4, bone morphogenetic protein 4 (BMP4)/Smad1/5/8 signaling pathway and isoflurane post-conditiong, which has effects on brain edema in rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Cerebral I/R injury was induced in rats by using the middle cerebral artery occlusion (MCAO) model for 90min, followed by 24h of reperfusion...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29023772/negative-modulation-of-the-gabaa-%C3%AF-1-receptor-function-by-l-cysteine
#6
Andrea N Beltrán González, Florencia Vicentini, Daniel J Calvo
L-Cysteine is an endogenous Sulphur containing amino acid with multiple and varied roles in the central nervous system, including neuroprotection and the maintenance of the redox balance. However, it was also suggested as an excitotoxic agent implicated in the pathogenesis of neurological disorders such as Parkinson's and Alzheimer's disease. L-Cysteine can modulate the activity of ionic channels, including voltage-gated calcium channels and glutamatergic NMDA receptors, whereas its effects on GABAergic neurotransmission had not been studied before...
October 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28969375/using-an-engineered-glutamate-gated-chloride-channel-to-silence-sensory-neurons-and-treat-neuropathic-pain-at-the-source
#7
Greg A Weir, Steven J Middleton, Alex J Clark, Tarun Daniel, Nikita Khovanov, Stephen B McMahon, David L Bennett
No abstract text is available yet for this article.
October 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28968469/effects-of-glutamate-and-ivermectin-on-single-glutamate-gated-chloride-channels-of-the-parasitic-nematode-h-contortus
#8
Mohammed Atif, Argel Estrada-Mondragon, Bindi Nguyen, Joseph W Lynch, Angelo Keramidas
Ivermectin (IVM) is a widely-used anthelmintic that works by binding to and activating glutamate-gated chloride channel receptors (GluClRs) in nematodes. The resulting chloride flux inhibits the pharyngeal muscle cells and motor neurons of nematodes, causing death by paralysis or starvation. IVM resistance is an emerging problem in many pest species, necessitating the development of novel drugs. However, drug optimisation requires a quantitative understanding of GluClR activation and modulation mechanisms. Here we investigated the biophysical properties of homomeric α (avr-14b) GluClRs from the parasitic nematode, H...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28924007/multiple-signaling-pathways-coordinately-regulate-forgetting-of-olfactory-adaptation-through-control-of-sensory-responses-in-caenorhabditis-elegans
#9
Tomohiro Kitazono, Sayuri Hara-Kuge, Osamu Matsuda, Akitoshi Inoue, Manabi Fujiwara, Takeshi Ishihara
Forgetting memories is important for animals to properly respond to continuously changing environments. To elucidate the mechanisms of forgetting, we used one of the behavioral plasticities of Caenorhabditis elegans hermaphrodite, olfactory adaptation to an attractive odorant, diacetyl, as a simple model of learning. In C. elegans, the TIR-1/JNK-1 pathway accelerates forgetting of olfactory adaptation by facilitating neural secretion from AWC sensory neurons. In this study, to identify the downstream effectors of the TIR-1/JNK-1 pathway, we conducted a genetic screen for suppressors of the gain-of-function mutant of tir-1 (ok1052), which shows excessive forgetting...
October 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28680296/distribution-and-function-of-the-bestrophin-1-best1-channel-in-the-brain
#10
REVIEW
Soo-Jin Oh, C Justin Lee
Bestrophin-1 (Best1) is a calcium-activated anion channel identified from retinal pigment epithelium where human mutations are associated with Best's macular degeneration. Best1 is known to be expressed in a variety of tissues including the brain, and is thought to be involved in many physiological processes. This review focuses on the current state of knowledge on aspects of expression and function of Best1 in the brain. Best1 protein is observed in cortical and hippocampal astrocytes, in cerebellar Bergmann glia and lamellar astrocytes, in thalamic reticular neurons, in meninges and in the epithelial cells of the choroid plexus...
June 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28611584/glial-and-neuronal-glutamate-transporters-differ-in-the-na-requirements-for-activation-of-the-substrate-independent-anion-conductance
#11
Christopher B Divito, Jenna E Borowski, Nathan G Glasgow, Aneysis D Gonzalez-Suarez, Delany Torres-Salazar, Jon W Johnson, Susan G Amara
Excitatory amino acid transporters (EAATs) are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na(+) and substrate binding. The activation of the anion channel by binding of Na(+) alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3) and EAAT4. To date, no difference has been observed for the substrate dependence of anion channel gating between the glial, EAAT1 and EAAT2, and the neuronal isoforms EAAT3, EAAT4 and EAAT5...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28575529/abnormal-%C3%AE-aminobutyric-acid-neurotransmission-in-a-kcnq2-model-of-early-onset-epilepsy
#12
Taku Uchida, Christoph Lossin, Yukiko Ihara, Masanobu Deshimaru, Yuchio Yanagawa, Susumu Koyama, Shinichi Hirose
OBJECTIVE: Mutations of the KCNQ2 gene, which encodes the Kv 7.2 subunit of voltage-gated M-type potassium channels, have been associated with epilepsy in the neonatal period. This developmental stage is unique in that the neurotransmitter gamma aminobutyric acid (GABA), which is inhibitory in adults, triggers excitatory action due to a reversed chloride gradient. METHODS: To examine whether KCNQ2-related neuronal hyperexcitability involves neonatally excitatory GABA, we examined 1-week-old knockin mice expressing the Kv 7...
August 2017: Epilepsia
https://www.readbyqxmd.com/read/28536821/impaired-motor-coordination-and-learning-in-mice-lacking-anoctamin-2-calcium-gated-chloride-channels
#13
Franziska Neureither, Katharina Ziegler, Claudia Pitzer, Stephan Frings, Frank Möhrlen
Neurons communicate through excitatory and inhibitory synapses. Both lines of communication are adjustable and allow the fine tuning of signal exchange required for learning processes in neural networks. Several distinct modes of plasticity modulate glutamatergic and GABAergic synapses in Purkinje cells of the cerebellar cortex to promote motor control and learning. In the present paper, we present evidence for a role of short-term ionic plasticity in the cerebellar circuit activity. This type of plasticity results from altered chloride driving forces at the synapses that molecular layer interneurons form on Purkinje cell dendrites...
May 23, 2017: Cerebellum
https://www.readbyqxmd.com/read/28528670/glycine-receptor-drug-discovery
#14
Joseph W Lynch, Yan Zhang, Sahil Talwar, Argel Estrada-Mondragon
Postsynaptic glycine receptor (GlyR) chloride channels mediate inhibitory neurotransmission in the spinal cord and brain stem, although presynaptic and extrasynaptic GlyRs are expressed more widely throughout the brain. In humans, GlyRs are assembled as homo- or heteromeric pentamers of α1-3 and β subunits. GlyR malfunctions have been linked to a range of neurological disorders including hyperekplexia, temporal lobe epilepsy, autism, breathing disorders, and chronic inflammatory pain. Although it is possible that GlyRs may eventually be clinically targeted for a variety of neurological disorders, most research to date has focused on developing GlyR-targeted treatments for chronic pain...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28514446/identification-of-preoptic-sleep-neurons-using-retrograde-labelling-and-gene-profiling
#15
Shinjae Chung, Franz Weber, Peng Zhong, Chan Lek Tan, Thuc Nghi Nguyen, Kevin T Beier, Nikolai Hörmann, Wei-Cheng Chang, Zhe Zhang, Johnny Phong Do, Shenqin Yao, Michael J Krashes, Bosiljka Tasic, Ali Cetin, Hongkui Zeng, Zachary A Knight, Liqun Luo, Yang Dan
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28496181/the-neuronal-k-cl-co-transporter-2-slc12a5-modulates-insulin-secretion
#16
Shams Kursan, Timothy S McMillen, Pavani Beesetty, Eduardo Dias-Junior, Mohammed M Almutairi, Abu A Sajib, J Ashot Kozak, Lydia Aguilar-Bryan, Mauricio Di Fulvio
Intracellular chloride concentration ([Cl(-)]i) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl(-) loaders such as the Na(+)K(+)2Cl(-) co-transporter 1 (Slc12a2) over Cl(-)extruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the "neuron-specific" K(+)Cl(-) co-transporter 2 (KCC2, Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where we provide evidence for its role in the insulin secretory response...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479061/crystal-structures-of-human-glyr%C3%AE-3-bound-to-ivermectin
#17
Xin Huang, Hao Chen, Paul L Shaffer
Ivermectin acts as a positive allosteric modulator of several Cys-loop receptors including the glutamate-gated chloride channels (GluCls), γ-aminobutyric acid receptors (GABAARs), glycine receptors (GlyRs), and neuronal α7-nicotinic receptors (α7 nAChRs). The crystal structure of Caenorhabditis elegans GluCl complexed with ivermectin revealed the details of its ivermectin binding site. Although the electron microscopy structure of zebrafish GlyRα1 complexed with ivermectin demonstrated a similar binding orientation, detailed structural information on the ivermectin binding and pore opening for Cys-loop receptors in vertebrates has been elusive...
June 6, 2017: Structure
https://www.readbyqxmd.com/read/28470528/phenotyping-cellular-viability-by-functional-analysis-of-ion-channels-glyr-targeted-screening-in-nt2-n-cells
#18
Katharina Kuenzel, Sepideh Abolpour Mofrad, Daniel F Gilbert
Glycine receptor chloride channels (GlyRs) are attractive drug targets for therapeutic intervention and are also more and more recognized in the context of in vitro neurotoxicity and developmental neurotoxicity testing. Assaying the functional properties of GlyR can serve as an indicator of cellular viability and the integrity of the developing and mature central nervous system. Human pluripotent NTERA-2 (NT2) stem cells undergo neuronal differentiation upon stimulation with retinoic acid and express a large variety of neuronal proteins-including GlyR...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28460564/effect-of-tpmpa-gabac-receptor-antagonist-on-neuronal-response-properties-in-rat-barrel-cortex
#19
Elham Mohammadi, Ali Shamsizadeh, Elham Salari, Iman Fatemi, Mohammad Allahtavakoli, Ali Roohbakhsh
GABAC receptors are ligand-gated chloride channels and have important roles in some neurological functions like vision. Recent investigations demonstrated that these receptors are also expressed in the somatosensory cortex. In this study, we investigated the effect of (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) (GABAC receptor antagonist) on the properties of the neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. Twenty-eight male Wistar rats, weighing 230-260 g, were used in this study...
May 1, 2017: Somatosensory & Motor Research
https://www.readbyqxmd.com/read/28420732/modulation-of-tmem16a-channel-activity-by-the-von-willebrand-factor-type-a-vwa-domain-of-the-calcium-activated-chloride-channel-regulator-1-clca1
#20
Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N Berry, Colin G Nichols, Tom J Brett
Calcium-activated chloride channels (CaCCs) are key players in transepithelial ion transport and fluid secretion, smooth muscle constriction, neuronal excitability, and cell proliferation. The CaCC regulator 1 (CLCA1) modulates the activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel at the cell surface, but the exact mechanism is unknown. Here we demonstrate that the von Willebrand factor type A (VWA) domain within the cleaved CLCA1 N-terminal fragment is necessary and sufficient for this interaction...
June 2, 2017: Journal of Biological Chemistry
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