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neuron and chloride channel

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https://www.readbyqxmd.com/read/29765304/chloride-homeostasis-in-neurons-with-special-emphasis-on-the-olivocerebellar-system-differential-roles-for-transporters-and-channels
#1
REVIEW
Negah Rahmati, Freek E Hoebeek, Saša Peter, Chris I De Zeeuw
The intraneuronal ionic composition is an important determinant of brain functioning. There is growing evidence that aberrant homeostasis of the intracellular concentration of Cl- ([Cl- ]i ) evokes, in addition to that of Na+ and Ca2+ , robust impairments of neuronal excitability and neurotransmission and thereby neurological conditions. More specifically, understanding the mechanisms underlying regulation of [Cl- ]i is crucial for deciphering the variability in GABAergic and glycinergic signaling of neurons, in both health and disease...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29738885/regulation-of-seizure-induced-mecp2-ser421-phosphorylation-in-the-developing-brain
#2
Evan C Rosenberg, Jocelyn J Lippman-Bell, Marcus Handy, Samantha S Soldan, Sanjay Rakhade, Cristina Hilario-Gomez, Kaitlyn Folweiler, Leah Jacobs, Frances E Jensen
Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of CaV 1.2 L-type voltage gated calcium (Ca2+ ) channels (LT-VGCCs) and Ca2+ -permeable AMPARs (CP-AMPARs) lacking GluA2 subunits. We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca2+ -dependent signaling pathways including that of methyl-CPG-binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome...
May 5, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29651138/gene-expression-links-functional-networks-across-cortex-and-striatum
#3
Kevin M Anderson, Fenna M Krienen, Eun Young Choi, Jenna M Reinen, B T Thomas Yeo, Avram J Holmes
The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29580953/effects-of-drugs-of-abuse-on-channelrhodopsin-2-kinetics
#4
Dominic Gioia, Minfu Xu, Wesley Wayman, John Woodward
Channelrhodopsins are light activated ion channels used extensively over the past decade to probe the function of genetically defined neuronal populations and distinct neural circuits with high temporal and spatial precision. The widely used Channelrhodopsin-2 variant (ChR2) is an excitatory opsin that undergoes conformational changes in response to blue light, allowing non-selective passage of protons and cations across the plasma membrane thus leading to depolarization. In the addiction neuroscience field, opsins such as ChR2 provide a means to disambiguate the overlapping circuitry involved in mediating the reinforcing and aversive effects of drugs of abuse as well as to determine the plasticity that can occur in these circuits during the development of dependence...
March 23, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29540815/computational-methods-for-estimating-molecular-system-from-membrane-potential-recordings-in-nerve-growth-cone
#5
Tatsuya Yamada, Makoto Nishiyama, Shigeyuki Oba, Henri Claver Jimbo, Kazushi Ikeda, Shin Ishii, Kyonsoo Hong, Yuichi Sakumura
Biological cells express intracellular biomolecular information to the extracellular environment as various physical responses. We show a novel computational approach to estimate intracellular biomolecular pathways from growth cone electrophysiological responses. Previously, it was shown that cGMP signaling regulates membrane potential (MP) shifts that control the growth cone turning direction during neuronal development. We present here an integrated deterministic mathematical model and Bayesian reversed-engineering framework that enables estimation of the molecular signaling pathway from electrical recordings and considers both the system uncertainty and cell-to-cell variability...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29503609/it-s-all-about-timing-the-involvement-of-kir4-1-channel-regulation-in-acute-ischemic-stroke-pathology
#6
REVIEW
Meagan Milton, Patrice D Smith
An acute ischemic stroke is characterized by the presence of a blood clot that limits blood flow to the brain resulting in subsequent neuronal loss. Acute stroke threatens neuronal survival, which relies heavily upon proper function of astrocytes. Neurons are more susceptible to cell death when an astrocyte is unable to carry out its normal functions in supporting the neuron in the area affected by the stroke (Rossi et al., 2007; Takano et al., 2009). For example, under normal conditions, astrocytes initially swell in response to changes in extracellular osmotic pressure and then reduce their regulatory volume in response to volume-activated potassium (K+ ) and chloride channels (Vella et al...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29500720/voltage-sensitive-calcium-channels-in-the-brain-relevance-to-alcohol-intoxication-and-withdrawal
#7
Prosper N'Gouemo
Voltage-sensitive Ca2+ (CaV ) channels are the primary route of depolarization-induced Ca2+ entry in neurons and other excitable cells, leading to an increase in intracellular Ca2+ concentration ([Ca2+ ]i ). The resulting increase in [Ca2+ ]i activates a wide range of Ca2+ -dependent processes in neurons, including neurotransmitter release, gene transcription, activation of Ca2+ -dependent enzymes, and activation of certain K+ channels and chloride channels. In addition to their key roles under physiological conditions, CaV channels are also an important target of alcohol, and alcohol-induced changes in Ca2+ signaling can disturb neuronal homeostasis, Ca2+ -mediated gene transcription, and the function of neuronal circuits, leading to various neurological and/or neuropsychiatric symptoms and disorders, including alcohol withdrawal induced-seizures and alcoholism...
March 3, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29479306/identification-of-chloride-channels-clcn3-and-clcn5-mediating-the-excitatory-cl-currents-activated-by-sphingosine-1-phosphate-in-sensory-neurons
#8
Yanmei Qi, Norbert Mair, Kai K Kummer, Michael G Leitner, María Camprubí-Robles, Michiel Langeslag, Michaela Kress
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl- current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29478917/the-sixth-transmembrane-segment-is-a-major-gating-component-of-the-tmem16a-calcium-activated-chloride-channel
#9
Christian J Peters, John M Gilchrist, Jason Tien, Neville P Bethel, Lijun Qi, Tingxu Chen, Lynn Wang, Yuh Nung Jan, Michael Grabe, Lily Y Jan
Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating...
March 7, 2018: Neuron
https://www.readbyqxmd.com/read/29460030/succinic-semialdehyde-dehydrogenase-deficiency-a-disorder-of-gaba-metabolism-an-update-on-pharmacological-and-enzyme-replacement-therapeutic-strategies
#10
Kara R Vogel, Garrett R Ainslie, Dana C Walters, Alice McConnell, Sameer C Dhamne, Alexander Rotenberg, Jean-Baptiste Roullet, K Michael Gibson
We present an update to the status of research on succinic semialdehyde dehydrogenase (SSADH) deficiency (SSADHD), a rare disorder of GABA metabolism. This is an unusual disorder featuring the accumulation of both GABA and its neuromodulatory analog, gamma-hydroxybutyric acid (GHB), and recent studies have advanced the potential clinical application of NCS-382, a putative GHB receptor antagonist. Animal studies have provided proof-of-concept that enzyme replacement therapy could represent a long-term therapeutic option...
February 19, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29439248/transient-receptor-potential-vanilloid-4-activation-induced-increase-in-glycine-activated-current-in-mouse-hippocampal-pyramidal-neurons
#11
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29364072/the-antihelminthic-moxidectin-enhances-tonic-gaba-currents-in-rodent-hippocampal-pyramidal-neurons
#12
Jay Spampanato, Anne Gibson, F Edward Dudek
Macrocyclic lactones (MLs) are commonly used treatments for parasitic worm and insect infections in humans, livestock and companion animals. MLs target the invertebrate glutamate-activated chloride channel that is not present in vertebrates. MLs are not entirely inert in vertebrates though; they have been reported to have activity in heterologous expression systems consisting of ligand-gated ion channels that are present in the mammalian central nervous system (CNS). However, these compounds are typically not able to reach significant concentrations in the CNS due to the activity of the blood-brain barrier P-glycoprotein extrusion system...
January 24, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29338612/gene-profiling-of-nucleus-basalis-tau-containing-neurons-in-chronic-traumatic-encephalopathy-a-chronic-effects-of-neurotrauma-consortium-study
#13
Elliott J Mufson, Bin He, Stephen D Ginsberg, Benjamin A Carper, Gayle S Bieler, Fiona Crawford, Victor E Alvarez, Bertrand R Huber, Thor D Stein, Ann C McKee, Sylvia E Perez
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increased number of NFTs across the pathological stages of CTE...
April 5, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29329909/the-signaling-role-for-chloride-in-the-bidirectional-communication-between-neurons-and-astrocytes
#14
REVIEW
Corinne S Wilson, Alexander A Mongin
It is well known that the electrical signaling in neuronal networks is modulated by chloride (Cl- ) fluxes via the inhibitory GABAA and glycine receptors. Here, we discuss the putative contribution of Cl- fluxes and intracellular Cl- to other forms of information transfer in the CNS, namely the bidirectional communication between neurons and astrocytes. The manuscript (i) summarizes the generic functions of Cl- in cellular physiology, (ii) recaps molecular identities and properties of Cl- transporters and channels in neurons and astrocytes, and (iii) analyzes emerging studies implicating Cl- in the modulation of neuroglial communication...
January 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29297130/key-role-of-external-chloride-ions-in-regulation-of-fast-sodium-channels-in-rat-cerebellum-purkinje-neurons
#15
V L Zamoyski, V V Grigoriev
A decrease in the external chloride ion concentration to 4 mM caused a decrease in the fast sodium current to 85-100% in rat cerebellum Purkinje neurons in the whole-cell configuration using the patchclamp method. This effect did not depend on the main cation from the internal side of the cell membrane (120 mM of potassium or cesium) and also appeared when Cl- was substituted with sulfate (SO2 -4 ) or phosphate (H2 PO4 - ) anion outside of the cell. The effect was reversible after washing out the low chloride by the standard saline...
November 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29273736/vglut1-functions-as-a-glutamate-proton-exchanger-with-chloride-channel-activity-in-hippocampal-glutamatergic-synapses
#16
Magalie Martineau, Raul E Guzman, Christoph Fahlke, Jürgen Klingauf
Glutamate is the major excitatory transmitter in the vertebrate nervous system. To maintain synaptic efficacy, recycling synaptic vesicles (SV) are refilled with glutamate by vesicular glutamate transporters (VGLUTs). The dynamics and mechanism of glutamate uptake in intact neurons are still largely unknown. Here, we show by live-cell imaging with pH- and chloride-sensitive fluorescent probes in cultured hippocampal neurons of wild-type and VGLUT1-deficient mice that in SVs VGLUT functions as a glutamate/proton exchanger associated with a channel-like chloride conductance...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29259251/bkip-1-an-auxiliary-subunit-critical-to-slo-1-function-inhibits-slo-2-potassium-channel-in-vivo
#17
Long-Gang Niu, Ping Liu, Yuan Shui, Roger Mailler, Zhao-Wen Wang, Bojun Chen
Auxiliary subunits are often needed to tailor K+ channel functional properties and expression levels. Many auxiliary subunits have been identified for mammalian Slo1, a high-conductance K+ channel gated by voltage and Ca2+ . Experiments with heterologous expression systems show that some of the identified Slo1 auxiliary subunits can also regulate other Slo K+ channels. However, it is unclear whether a single auxiliary subunit may regulate more than one Slo channel in native tissues. BKIP-1, an auxiliary subunit of C...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29236691/activation-mechanism-of-the-calcium-activated-chloride-channel-tmem16a-revealed-by-cryo-em
#18
Cristina Paulino, Valeria Kalienkova, Andy K M Lam, Yvonne Neldner, Raimund Dutzler
The calcium-activated chloride channel TMEM16A is a ligand-gated anion channel that opens in response to an increase in intracellular Ca2+ concentration. The protein is broadly expressed and contributes to diverse physiological processes, including transepithelial chloride transport and the control of electrical signalling in smooth muscles and certain neurons. As a member of the TMEM16 (or anoctamin) family of membrane proteins, TMEM16A is closely related to paralogues that function as scramblases, which facilitate the bidirectional movement of lipids across membranes...
December 21, 2017: Nature
https://www.readbyqxmd.com/read/29236684/cryo-em-structures-of-the-tmem16a-calcium-activated-chloride-channel
#19
Shangyu Dang, Shengjie Feng, Jason Tien, Christian J Peters, David Bulkley, Marco Lolicato, Jianhua Zhao, Kathrin Zuberbühler, Wenlei Ye, Lijun Qi, Tingxu Chen, Charles S Craik, Yuh Nung Jan, Daniel L Minor, Yifan Cheng, Lily Yeh Jan
Calcium-activated chloride channels (CaCCs) encoded by TMEM16A control neuronal signalling, smooth muscle contraction, airway and exocrine gland secretion, and rhythmic movements of the gastrointestinal system. To understand how CaCCs mediate and control anion permeation to fulfil these physiological functions, knowledge of the mammalian TMEM16A structure and identification of its pore-lining residues are essential. TMEM16A forms a dimer with two pores. Previous CaCC structural analyses have relied on homology modelling of a homologue (nhTMEM16) from the fungus Nectria haematococca that functions primarily as a lipid scramblase, as well as subnanometre-resolution electron cryo-microscopy...
December 21, 2017: Nature
https://www.readbyqxmd.com/read/29186788/neurotoxic-effects-of-linalool-and-%C3%AE-pinene-on-tribolium-castaneum-herbst
#20
Nerlis Pajaro-Castro, Karina Caballero-Gallardo, Jesus Olivero-Verbel
Effective, ethical pest control requires the use of chemicals that are highly specific, safe, and ecofriendly. Linalool and β-pinene occur naturally as major constituents of the essential oils of many plant species distributed throughout the world, and thus meet these requirements. These monoterpenes were tested as repellents against Tribolium castaneum , using the area preference method, after four hours of exposure and the effect transcriptional of genes associated with neurotransmission. Changes in gene expression of acetylcholinesterase (Ace1), GABA-gated anion channel splice variant 3a6a (Rdl), GABA-gated ion channel (Grd), glutamate-gated chloride channel (Glucl), and histamine-gated chloride channel 2 (Hiscl2) were assessed and the interaction with proteins important for the insect using in silico methods was also studied...
November 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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