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neuron and chloride channel

Laurence D Picton, Keith T Sillar
Dopamine plays important roles in the development and modulation of motor control circuits. Here we show that dopamine exerts potent effects on the central pattern generator circuit controlling locomotory swimming in post-embryonic Xenopus tadpoles. Dopamine (0.5-100 μM) reduced fictive swim bout occurrence and caused both spontaneous and evoked episodes to become shorter, slower and weaker. The D2-like receptor agonist quinpirole mimicked this repertoire of inhibitory effects on swimming, whilst the D4 receptor antagonist, L745,870, had the opposite effects...
October 20, 2016: Scientific Reports
Priyanka D Abeyrathne, Mohamed Chami, Henning Stahlberg
The chloride channel (ClC) protein family comprises both chloride (Cl(-)) channels and chloride/proton (Cl(-)/H(+)) antiporters. In prokaryotes and eukaryotes, these proteins mediate the movement of Cl(-) ions across the membrane. In eukaryotes, ClC proteins play a role in the stabilization of membrane potential, epithelial ion transport, hippocampal neuroprotection, cardiac pacemaker activity and vesicular acidification. Moreover, mutations in the genes encoding ClC proteins can cause genetic disease in humans...
September 2016: Biochimie
Isabella Salzer, Enkhbileg Gantumur, Arsalan Yousuf, Stefan Boehm
Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by 5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons dissociated from rat DRGs were used to investigate effects of 5HT on membrane excitability and currents through ligand- as well as voltage-gated ion channels. In 58% of the neurons tested, 5HT increased action potential firing, an effect that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the 5HT3 antagonist tropisetron...
November 2016: Neuropharmacology
Ruiqi Xue, Huan Gu, Yamei Qiu, Yong Guo, Christine Korteweg, Jin Huang, Jiang Gu
CF is caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) which is an anion selective transmembrane ion channel that mainly regulates chloride transport, expressed in the epithelia of various organs. Recently, we have demonstrated CFTR expression in the brain, the spinal cord and the sympathetic ganglia. This study aims to investigate the expression and distribution of CFTR in the ganglia of the human gastrointestinal tract. Fresh tissue and formalin-fixed paraffin-embedded normal gastrointestinal tract samples were collected from eleven surgical patients and five autopsy cases...
2016: Scientific Reports
Rui-Ping Pang, Man-Xiu Xie, Jie Yang, Kai-Feng Shen, Xi Chen, Ying-Xue Su, Chao Yang, Jing Tao, Si-Jia Liang, Jia-Guo Zhou, He-Quan Zhu, Xu-Hong Wei, Yong-Yong Li, Zhi-Hai Qin, Xian-Guo Liu
ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, while overexpression of ClC-3 reversed the hypersensitivity to mechanical stimuli after peripheral nerve injury...
November 2016: Neuropharmacology
Katharina Kuenzel, Oliver Friedrich, Daniel F Gilbert
GABAARs and GlyRs are considered attractive drug targets for therapeutic intervention and are also increasingly recognized in the context of in vitro neurotoxicity (NT) and developmental neurotoxicity (DNT) testing. However, systematic human-specific GABAAR and GlyR-targeted drug screening and toxicity testing is hampered due to lack of appropriate in vitro models that express native GABAARs and GlyRs. We have established a human pluripotent stem cell line (NT2) stably expressing YFP-I152L, a halide-sensitive variant of yellow fluorescent protein (YFP), allowing for fluorescence-based functional analysis of chloride channels...
2016: Frontiers in Molecular Neuroscience
S C Song, J A Beatty, C J Wilson
Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked. In the depolarized state, whether spontaneous or induced by sodium channel blockade, the neurons express a 3- to 7-Hz oscillation and membrane impedance resonance in the same frequency range. The membrane potential oscillation and membrane resonance are expressed in the same voltage range (greater than -40 mV). We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed green fluorescent protein under the control of the neuropeptide Y promoter...
October 1, 2016: Journal of Neurophysiology
S E Boronovsky, Y R Nartsissov
Our study reports computer software that simulates the work of a single glycine receptor (GlyR). GlyRs have been found in various types of tissues, but their most important role seems to be in neurons, where they hyperpolarise membranes by opening chloride transmembrane channels. The software is based on a combination of two blocks. One block describes the Brownian dynamics of charged particle motion in a dielectric medium, and the other block determines the probability and timing of receptor activation. Using this software, the voltage-current dependencies and time curves of the transmembrane current were obtained...
July 2016: Bulletin of Mathematical Biology
Wei Wang, Li Gu, Alexei Verkhratsky, Liang Peng
Hyperammonemia occurring following acute liver failure is the primary cause of hepatic encephalopathy. In the brain, ammonium is catabolised by glutamine synthetase expressed exclusively in astroglia; ammonium overload impairs astroglial homeostatic systems. Previously, we had reported that chronic treatment with 3 mM ammonia increased expression of transient receptor potential canonic 1 (TRPC1) channels and Ca(2+) release from intracellular Ca(2+) stores (Liang et al. in Neurochem Res 39:2127-2135, 2014)...
July 14, 2016: Neurochemical Research
Negah Rahmati, Maria Fernanda Vinueza Veloz, Jie Xu, Sharon Barone, Nahuel Rodolfo Ben Hamida, Martijn Schonewille, Freek E Hoebeek, Manoocher Soleimani, Chris I De Zeeuw
Chloride homeostasis determines the impact of inhibitory synaptic transmission and thereby mediates the excitability of neurons. Even though cerebellar Purkinje cells (PCs) receive a pronounced inhibitory GABAergic input from stellate and basket cells, the role of chloride homeostasis in these neurons is largely unknown. Here we studied at both the cellular and systems physiological level the function of a recently discovered chloride channel, SLC26A11 or kidney brain anion transporter (KBAT), which is prominently expressed in PCs...
May 2016: ENeuro
Constanze Raltschev, Florian Hetsch, Aline Winkelmann, Jochen C Meier, Marcus Semtner
Glycine receptors are chloride-permeable, ligand-gated ion channels and contribute to the inhibition of neuronal firing in the central nervous system or to facilitation of neurotransmitter release if expressed at presynaptic sites. Recent structure-function studies have provided detailed insights into the mechanisms of channel gating, desensitization, and ion permeation. However, most of the work has focused only on comparing a few isoforms, and among studies, different cellular expression systems were used...
August 19, 2016: Journal of Biological Chemistry
Daniel Feingold, Tanja Starc, Michael J O'Donnell, Laura Nilson, Joseph A Dent
Pentameric ligand-gated ion channels (pLGICs) constitute a large protein superfamily in metazoa whose role as neurotransmitter receptors mediating rapid, ionotropic synaptic transmission has been extensively studied. Although the vast majority of pLGICs appear to be neurotransmitter receptors, the identification of pLGICs in non-neuronal tissues and homologous pLGIC-like proteins in prokaryotes points to biological functions, possibly ancestral, that are independent of neuronal signalling. Here, we report the molecular and physiological characterization of a highly divergent, orphan pLGIC subunit encoded by the pHCl-2 (CG11340) gene, in Drosophila melanogaster We show that pHCl-2 forms a channel that is insensitive to a wide array of neurotransmitters, but is instead gated by changes in extracellular pH...
September 1, 2016: Journal of Experimental Biology
Xiao-Xue Zhang, Xiao-Chun Min, Xu-Lin Xu, Min Zheng, Lian-Jun Guo
The selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD7288) blocks the induction of long-term potentiation in the perforant path-CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path-CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca(2+) concentration [Ca(2+)]i) using Fura-2...
May 2016: Neural Regeneration Research
Makoto Tominaga
Capsaicin receptor TRPV1 and wasabi receptor TRPA1 are expressed in the unmyelinated C fiber nociceptors and activated by various nociceptive stimuli causing pain in our body. Their involvement in nociception was proven with behavior studies using mice lacking TRPV1 and TRPA1. TRPV1 was found to interact with a calcium-activated chloride channel, anoctamin1 (ANO1), and calcium ions entering the primary sensory neurons activated ANO1, leading to chloride efflux which resulted in further depolarization. This is a novel pain-enhancing mechanism...
April 2016: Nihon Shinkei Seishin Yakurigaku Zasshi, Japanese Journal of Psychopharmacology
Michaela Meyer, Sameer C Dhamne, Christopher M LaCoursiere, Dimira Tambunan, Annapurna Poduri, Alexander Rotenberg
Zebrafish epilepsy models are emerging tools in experimental epilepsy. Zebrafish larvae, in particular, are advantageous because they can be easily genetically altered and used for developmental and drug studies since agents applied to the bath penetrate the organism easily. Methods for electrophysiological recordings in zebrafish are new and evolving. We present a novel multi-electrode array method to non-invasively record electrical activity from up to 61 locations of an intact larval zebrafish head. This method enables transcranial noninvasive recording of extracellular field potentials (which include multi-unit activity and EEG) to identify epileptic seizures...
2016: PloS One
Sungmo Park, Emily E Kramer, Valentina Mercaldo, Asim J Rashid, Nathan Insel, Paul W Frankland, Sheena A Josselyn
The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability (Han et al, 2009; Zhou et al, 2009; Choi et al, 2011; Sano et al, 2014). Here we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory...
May 17, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jianguo Li, Quanzhong Chang, Xiaoming Li, Xiawen Li, Jiantian Qiao, Tianming Gao
Cerebral ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms remain unclear, but it is known that apoptosis is involved in this process. Chloride efflux has been implicated in the progression of apoptosis in various cell types. Using both the inside-out and whole-cell configurations of the patch-clamp technique, the present study characterized an outwardly rectifying chloride channel (ORCC) in acutely dissociated pyramid neurons in the hippocampus of adult rats...
August 1, 2016: Brain Research
Emily J Remnant, Adam Williams, Chris Lumb, Ying Ting Yang, Janice Chan, Sebastian Duchêne, Phillip J Daborn, Philip Batterham, Trent Perry
Ligand-gated chloride channels have established roles in inhibitory neurotransmission in the nervous systems of vertebrates and invertebrates. Paradoxically, expression databases in Drosophila melanogaster have revealed that three uncharacterized ligand-gated chloride channel subunits, CG7589, CG6927, and CG11340, are highly expressed in nonneuronal tissues. Furthermore, subunit copy number varies between insects, with some orders containing one ortholog, whereas other lineages exhibit copy number increases...
2016: G3: Genes—Genomes—Genetics
Doodipala Samba Reddy, William A Estes
Neurosteroids are key endogenous molecules in the brain that affect many neural functions. We describe here recent advances in US National Institutes of Health (NIH)-sponsored and other clinical studies of neurosteroids for CNS disorders. The neuronal GABA-A receptor chloride channel is one of the prime molecular targets of neurosteroids. Allopregnanolone-like neurosteroids are potent allosteric agonists as well as direct activators of both synaptic and extrasynaptic GABA-A receptors. Hence, neurosteroids can maximally enhance synaptic phasic and extrasynaptic tonic inhibition...
July 2016: Trends in Pharmacological Sciences
Juan A Contreras-Vite, Silvia Cruz-Rangel, José J De Jesús-Pérez, Iván A Aréchiga Figueroa, Aldo A Rodríguez-Menchaca, Patricia Pérez-Cornejo, H Criss Hartzell, Jorge Arreola
TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca(2+)]i), membrane depolarization, extracellular Cl(-) or permeant anions and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations...
July 2016: Pflügers Archiv: European Journal of Physiology
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