Academic literature on the topic 'GABA Ions chlorure'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'GABA Ions chlorure.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "GABA Ions chlorure"
1
Feigenspan, Andreas, and Reto Weiler. "Electrophysiological Properties of Mouse Horizontal Cell GABAA Receptors." Journal of Neurophysiology 92, no. 5 (November 2004): 2789–801. http://dx.doi.org/10.1152/jn.00284.2004.
Full textAbstract:
GABA-induced currents have been characterized in isolated horizontal cells from lower vertebrates but not in mammalian horizontal cells. Therefore horizontal cells were isolated after enzymatical and mechanical dissociation of the adult mouse retina and visually identified. We recorded from horizontal cell bodies using the whole cell and outside-out configuration of the patch-clamp technique. Extracellular application of GABA induced inward currents carried by chloride ions. GABA-evoked currents were completely and reversibly blocked by the competitive GABAA receptor antagonist bicuculline (IC50 = 1.7 μM), indicating expression of GABAA but not GABAC receptors. Their affinity for GABA was moderate (EC50 = 30 μM), and the Hill coefficient was 1.3, corresponding to two GABA binding sites. GABA responses were partially reduced by picrotoxin with differential effects on peak and steady-state current values. Zinc blocked the GABA response with an IC50 value of 7.3 μM in a noncompetitive manner. Furthermore, GABA receptors of horizontal cells were modulated by extracellular application of diazepam, zolpidem, methyl 6,7-dimethoxy-4-ethyl-β-carboxylate, pentobarbital, and alphaxalone, thus showing typical pharmacological properties of CNS GABAA receptors. GABA-evoked single-channel currents were characterized by a main conductance state of 29.8 pS and two subconductance states (20.2 and 10.8 pS, respectively). Kinetic analysis of single-channel events within bursts revealed similar mean open and closed times for the main conductance and the 20.2-pS subconductance state, resulting in open probabilities of 44.6 and 42.7%, respectively. The ratio of open to closed times, however, was significantly different for the 10.8-pS subconductance state with an open probability of 57.2%.
2
Laroute, Valérie, Roberto Mazzoli, Pascal Loubière, Enrica Pessione, and Muriel Cocaign-Bousquet. "Environmental Conditions Affecting GABA Production in Lactococcus lactis NCDO 2118." Microorganisms 9, no. 1 (January 7, 2021): 122. http://dx.doi.org/10.3390/microorganisms9010122.
Full textAbstract:
GABA (γ-aminobutyric acid) production has been widely described as an adaptive response to abiotic stress, allowing bacteria to survive in harsh environments. This work aimed to clarify and understand the relationship between GABA production and bacterial growth conditions, with particular reference to osmolarity. For this purpose, Lactococcus lactis NCDO 2118, a GABA-producing strain, was grown in glucose-supplemented chemically defined medium containing 34 mM L-glutamic acid, and different concentrations of salts (chloride, sulfate or phosphate ions) or polyols (sorbitol, glycerol). Unexpectedly, our data demonstrated that GABA production was not directly related to osmolarity. Chloride ions were the most significant factor influencing GABA yield in response to acidic stress while sulfate ions did not enhance GABA production. We demonstrated that the addition of chloride ions increased the glutamic acid decarboxylase (GAD) synthesis and the expression of the gadBC genes. Finally, under fed-batch conditions in a complex medium supplemented with 0.3 M NaCl and after a pH shift to 4.6, L. lactis NCDO 2118 was able to produce up to 413 mM GABA from 441 mM L-glutamic acid after only 56 h of culture, revealing the potential of L. lactis strains for intensive production of this bioactive molecule.
3
Sallard, Erwan, Diane Letourneur, and Pascal Legendre. "Electrophysiology of ionotropic GABA receptors." Cellular and Molecular Life Sciences 78, no. 13 (June 1, 2021): 5341–70. http://dx.doi.org/10.1007/s00018-021-03846-2.
Full textAbstract:
AbstractGABAA receptors are ligand-gated chloride channels and ionotropic receptors of GABA, the main inhibitory neurotransmitter in vertebrates. In this review, we discuss the major and diverse roles GABAA receptors play in the regulation of neuronal communication and the functioning of the brain. GABAA receptors have complex electrophysiological properties that enable them to mediate different types of currents such as phasic and tonic inhibitory currents. Their activity is finely regulated by membrane voltage, phosphorylation and several ions. GABAA receptors are pentameric and are assembled from a diverse set of subunits. They are subdivided into numerous subtypes, which differ widely in expression patterns, distribution and electrical activity. Substantial variations in macroscopic neural behavior can emerge from minor differences in structure and molecular activity between subtypes. Therefore, the diversity of GABAA receptors widens the neuronal repertoire of responses to external signals and contributes to shaping the electrical activity of neurons and other cell types.
4
Blanton, M. G., and A. R. Kriegstein. "Properties of amino acid neurotransmitter receptors of embryonic cortical neurons when activated by exogenous and endogenous agonists." Journal of Neurophysiology 67, no. 5 (May 1, 1992): 1185–200. http://dx.doi.org/10.1152/jn.1992.67.5.1185.
Full textAbstract:
1. The properties of receptors for amino acid neurotransmitters expressed by developing cortical neurons were studied with the use of whole-cell recording in the intact cerebral cortex of embryonic turtles in vitro. The inhibitory agonist gamma-aminobutyric acid (GABA) and the excitatory agonist glutamate were focally applied to single cells under voltage clamp, and the ionic dependence, voltage dependence, and pharmacological sensitivity of the responses were characterized. The responses mediated by a glutamate receptor subtype, the N-methyl-D-aspartate (NMDA) receptor, produced by glutamate and by evoked release of an endogenous excitatory agonist, were compared further. Fluctuation analysis was used to characterize the properties of the NMDA channels and the mechanism of action of receptor antagonists. 2. When postmitotic neurons first appeared at stage 15, all neurons tested responded to GABA with a current that reversed at the equilibrium potential for chloride ions and that was sensitive to the GABAA receptor antagonist bicuculline methiodide (BMI). As development proceeded, an increasing proportion of neurons also responded with a BMI-insensitive current that reversed near the equilibrium potential for potassium ions. This current was blocked by the GABAB receptor antagonist 3-amino-2-propyl phosponic acid (phaclofen). The GABAB agonist baclofen, however, failed to produce a detectable postsynaptic current. 3. Neurons at stage 15 showed a biphasic response to glutamate that reversed at the equilibrium potential for cations. All neurons tested showed a slow, sustained response associated with an increase in current variance compared with background, and, as development proceeded, an increasing proportion also exhibited a fast, transient response. Both fast and slow responses varied linearly with voltage in the absence of Mg2+ ions, but the addition of Mg2+ ions to the bathing medium attenuated the slow response at hyperpolarized potentials. As a result, the current-voltage relation of the slow response in the presence of Mg2+ ions exhibited a region of negative slope conductance, like that of currents mediated by NMDA receptors. 4. The fast and slow responses to glutamate differed in their pharmacological sensitivity. The fast responses were sensitive to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas the slow responses were sensitive to the NMDA receptor antagonist D(-)-2-amino-5-phosphonovalerate (D-APV). 5. When cells were held at -70 mV, glutamate evoked a fluctuating current consisting of channel currents with a mean open time, tau, of 4.42 +/- 0.47 (SE) ms in early postmitotic neurons at stage 15 and 4.99 +/- 0.38 ms at stages 17-20.(ABSTRACT TRUNCATED AT 400 WORDS)
5
Feigenspan, Andreas, Stefano Gustincich, and Elio Raviola. "Pharmacology of GABAA Receptors of Retinal Dopaminergic Neurons." Journal of Neurophysiology 84, no. 4 (October 1, 2000): 1697–707. http://dx.doi.org/10.1152/jn.2000.84.4.1697.
Full textAbstract:
When the vertebrate retina is stimulated by light, a class of amacrine or interplexiform cells release dopamine, a modulator responsible for neural adaptation to light. In the intact retina, dopamine release can be pharmacologically manipulated with agonists and antagonists at GABAA receptors, and dopaminergic (DA) cells receive input from GABAergic amacrines. Because there are only 450 DA cells in each mouse retina and they cannot be distinguished in the living state from other cells on the basis of their morphology, we used transgenic technology to label DA cells with human placental alkaline phosphatase, an enzyme that resides on the outer surface of the cell membrane. We could therefore identify DA cells in vitro after dissociation of the retina and investigate their activity with whole cell voltage clamp. We describe here the pharmacological properties of the GABAA receptors of solitary DA cells. GABA application induces a large inward current carried by chloride ions. The receptors are of the GABAA type because the GABA-evoked current is blocked by bicuculline. Their affinity for GABA is very high with an EC50 value of 7.4 μM. Co-application of benzodiazepine receptor ligands causes a strong increase in the peak current induced by GABA (maximal enhancement: CL-218872 220%; flunitrazepam 214%; zolpidem 348%) proving that DA cells express a type I benzodiazepine-receptor (BZ1). GABA-evoked currents are inhibited by Zn2+ with an IC50 of 58.9 ± 8.9 μM. Furthermore, these receptors are strongly potentiated by the modulator alphaxalone with an EC50 of 340 ± 4 nM. The allosteric modulator loreclezole increases GABA receptor currents by 43% (1 μM) and by 107% (10 μM). Using outside-out patches, we measured in single-channel recordings a main conductance (29 pS) and two subconductance (20 and 9 pS) states. We have previously shown by single-cell RT-PCR and immunocytochemistry that DA cells express seven different GABAA receptor subunits (α1, α3, α4, β1, β3, γ1, γ2S, and γ2L) and by immunocytochemistry that all subunits are expressed in the intact retina. We show here that at least α1, β3 and γ2 subunits are assembled into functional receptors.
6
Rudolph, Uwe. "Identification of Molecular Substrate for the Attenuation of Anxiety: A Step Toward the Development of Better Anti-Anxiety Drugs." Scientific World JOURNAL 1 (2001): 192–93. http://dx.doi.org/10.1100/tsw.2001.33.
Full textAbstract:
Anxiety disorders affect some 19 million people in the U.S. alone, costing $46.6 billion, or one third of the nation’s total mental health bill in 1990. Benzodiazepine tranquilizers like the prototypic diazepam are among the most widely used anti-anxiety agents. In addition to their anxiolytic action, they also induce sedation and may impair motor coordination, both of which are undesired side effects when they are used as anxiolytics. Not surprisingly, road traffic accidents may be increased for patients on classical benzodiazepines. In addition, these drugs carry the risk of dependence liability. Benzodiazepines augment the action of the inhibitory neurotransmitter g-aminobutyric acid (GABA) at contact points between two nerve cells called synapses, points at which information is transmitted from one nerve cell to the next. Synaptically released GABA binds to postsynaptic GABAA receptors, thus causing an influx of negatively charged chloride ions into the postsynaptic neuron. This leads to a hyperpolarization and thus functional inhibition of the postsynaptic cell. Benzodiazepines bind to a site on the GABAAreceptor which is different from the GABA binding site, thus increasing the chloride current. Benzodiazepines like diazepam bind to GABAAreceptors containing the α subunits α1, α2, α3, or α5, most likely in abgabg combinations.
7
Blaxter, Timothy J., and Peter L. Carlen. "GABA responses in rat dentate granule neurons are mediated by chloride." Canadian Journal of Physiology and Pharmacology 66, no. 5 (May 1, 1988): 637–42. http://dx.doi.org/10.1139/y88-099.
Full textAbstract:
The dendrites of granule cells in hippocampal slices responded to γ-aminobutyric acid (GABA) with a depolarization. The response was blocked by picrotoxin in a noncompetitive manner. Reductions in the extracellular chloride ion concentration changed the reversal potential of the response by an amount predicted from the Nernst equation for chloride ion. Chloride-dependent hyperpolarizing responses were sometimes also found in the cell body of the granule cells. Since the reversal potential followed that predicted from the Nernst equation for chloride, we conclude that the response was mediated by chloride ions alone with no contribution from other ions. This has not previously been shown for the depolarizing response to GABA in central neurons.
8
Hilgemann, Donald W., and Chin-Chih Lu. "Gat1 (Gaba:Na+:Cl−) Cotransport Function." Journal of General Physiology 114, no. 3 (September 1, 1999): 459–76. http://dx.doi.org/10.1085/jgp.114.3.459.
Full textAbstract:
We have developed an alternating access transport model that accounts well for GAT1 (GABA:Na+:Cl−) cotransport function in Xenopus oocyte membranes. To do so, many alternative models were fitted to a database on GAT1 function, and discrepancies were analyzed. The model assumes that GAT1 exists predominantly in two states, Ein and Eout. In the Ein state, one chloride and two sodium ions can bind sequentially from the cytoplasmic side. In the Eout state, one sodium ion is occluded within the transporter, and one chloride, one sodium, and one γ-aminobutyric acid (GABA) molecule can bind from the extracellular side. When Ein sites are empty, a transition to the Eout state opens binding sites to the outside and occludes one extracellular sodium ion. This conformational change is the major electrogenic GAT1 reaction, and it rate-limits forward transport (i.e., GABA uptake) at 0 mV. From the Eout state, one GABA can be translocated with one sodium ion to the cytoplasmic side, thereby forming the *Ein state. Thereafter, an extracellular chloride ion can be translocated and the occluded sodium ion released to the cytoplasm, which returns the transporter to the Ein state. GABA–GABA exchange can occur in the absence of extracellular chloride, but a chloride ion must be transported to complete a forward transport cycle. In the reverse transport cycle, one cytoplasmic chloride ion binds first to the Ein state, followed by two sodium ions. One chloride ion and one sodium ion are occluded together, and thereafter the second sodium ion and GABA are occluded and translocated. The weak voltage dependence of these reactions determines the slopes of outward current–voltage relations. Experimental results that are simulated accurately include (a) all current–voltage relations, (b) all substrate dependencies described to date, (c) cis–cis and cis–trans substrate interactions, (d) charge movements in the absence of transport current, (e) dependencies of charge movement kinetics on substrate concentrations, (f) pre–steady state current transients in the presence of substrates, (g) substrate-induced capacitance changes, (h) GABA–GABA exchange, and (i) the existence of inward transport current and GABA–GABA exchange in the nominal absence of extracellular chloride.
9
Katchman, A. N., S. Vicini, and N. Hershkowitz. "Mechanism of early anoxia-induced suppression of the GABAA-mediated inhibitory postsynaptic current." Journal of Neurophysiology 71, no. 3 (March 1, 1994): 1128–38. http://dx.doi.org/10.1152/jn.1994.71.3.1128.
Full textAbstract:
1. We investigated the mechanism of hypoxia-induced depression of gamma-aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons of hippocampal slices from 21- to 28-day-old rats. Cells were examined by whole-cell patch-clamp recording and hypoxia was induced by switching perfusion of the slice from oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2-5% CO2. 2. Synaptic responses evoked by stimulation of the Schaffer collateral-commissural projection at a fixed holding potential (VH = -60 mV) during anoxia revealed that the IPSC appeared more sensitive than the excitatory postsynaptic current to anoxia-induced depression. All subsequent studies examined the GABAA-mediated IPSC synaptic responses in isolation by direct stimulation of GABA interneurons in the stratum radiatum in the presence of extracellular 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) (20 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (50 microM) to block glutamatergic currents and intracellular QX-314 (lidocaine N-ethyl bromide, 1 mM) to block GABAB-mediated currents. When studied in this manner (VH = -60 mV) the GABAA-mediated IPSC appeared to change from an outward to inward current after exposure to anoxia. 3. The current-voltage relationship of GABAA-mediated IPSCs revealed that these changes resulted from a positive shift in the IPSC reversal potential without a significant change in the conductance. Thus under patch clamp apparent IPSC inhibition may result from a decrease in the extracellular concentration of chloride ions. Similar findings were observed with micropipettes that contained high intracellular chloride concentrations. 4. Miniature spontaneous IPSCs were examined in the presence of tetrodotoxin (1 microM) with micropipettes containing high intracellular chloride concentrations. The miniature IPSCs (mIPSCs) appeared as spontaneous transient inward currents. Consistent with an anoxia-induced decrease in extracellular chloride, the mean amplitude of the mIPSCs increased after the onset of anoxia. A significant decrease in rise and decay time was also noted during anoxia. The frequency of the mIPSCs also increased by approximately 300%. 5. The resting input resistance of the cells was examined by measuring the current resulting from a 20-mV hyperpolarizing pulse. A significant reduction in resistance was observed 2 min after the onset of anoxia. This still occurred, although to a lesser degree, in the presence of glutamatergic blockers (20 microM CPP plus 50 microM CNQX). In the presence of both GABAergic (picrotoxin, 100 microM) and glutamatergic blockers no significant reduction in resting input resistance was apparent after 2 min of anoxia.(ABSTRACT TRUNCATED AT 400 WORDS)
10
Poisbeau, P. "Pharmacologie des anxiolytiques." European Psychiatry 30, S2 (November 2015): S8. http://dx.doi.org/10.1016/j.eurpsy.2015.09.032.
Full textAbstract:
La cible principale des anxiolytiques est le récepteur-canal GABAA. Constitué de 5 sous-unités protéiques (majoritairement 2 alpha, 2 bêta, 1 gamma dans le système nerveux), il devient perméable aux ions chlorures après fixation d’au moins deux molécules d’acide gamma-aminobutyrique (GABA). Certains anxiolytiques, comme les benzodiazépines ou l’étifoxine, sont des modulateurs allostériques : ils augmentent cette perméabilité et renforcent ainsi l’inhibition des neurones qui expriment le récepteur GABAA. Le site de liaison des benzodiazépines est bien connu. À distance du site agoniste pour le GABA, il se situe à l’interface entre les sous-unités alpha gamma du récepteur. Notons que le zolpidem, une molécule non benzodiazépinique, se fixe également sur ce site avec une très haute affinité. Dans la classe des anxiolytiques, le chlorhydrate d’étifoxine (laboratoire Biocodex, Gentilly, France) occupe une place intéressante. L’étifoxine n’est pas une benzodiazépine et se fixe sur les sous-unités bêta du récepteur (bêta 2 > bêta 3). Ceci pourrait expliquer pourquoi son activité anxiolytique n’est pas associée à des manifestations indésirables comme la sédation, les troubles mnésiques et la tolérance fonctionnelle. Ainsi, lors de l’arrêt des traitements aucune pharmacodépendance n’est observée. L’étifoxine exerce également une action originale sur la mitochondrie en renforçant les systèmes cellulaires de neuroprotection et en favorisant la production d’un anxiolytique endogène, l’alloprégnanolone. L’alloprégnanolone est à ce jour le plus puissant stimulateur endogène connu de la fonction inhibitrice du récepteur GABAA. Nos travaux récents chez l’animal montrent les effets de cette double action sur les troubles anxieux et dépressif induits par la douleur neuropathique. Ils mettent également en évidence l’intérêt de la molécule pour soulager les symptômes douloureux périphériques dans de nombreux modèles de douleurs.
Dissertations / Theses on the topic "GABA Ions chlorure"
1
Roux, Sébastien. "Autisme et cervelet : le gradient des ions chlorures en question." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ030/document.
Full textAbstract:
Les objectifs de ma thèse ont été de caractériser le développement du gradient en ions chlorures dans les cellules de Purkinje dans un modèle d'étude de l'autisme : les souris exposées de façon prénatale au valproate de sodium. A cette fin, j'ai effectué des mesures éléctrophysiologiques de courants GABAergiques au cours du développement post-natal de ces animaux et des observations histologiques de la densité linéaire en cellules de Purkinje. D'autre part, j'ai participé à une étude comportementale visant à étudier l'influence d'un composé modulant le gradient en ions chlorures dans deux modèles génétiques d'étude de l'autisme : les souris Oprm1-/- et les souris Fmr1-/-. Au cours de ma thèse, j'ai mis en évidence un retard du développement du gradient en ions chlorures. J'ai également montré qu'une exposition prénatale au valproate de sodium induisait une perte post-natale en cellules de Purkinje. Enfin, le composé avec lequel j'ai travaillé améliore le phénotype autistique et laisse entrevoir un fort potentiel translationnelThe aims of my PhD were to characterize the development of the chloride gradient in Purkinje cells in a model of autism: mice prenatally exposed to sodium valproate. To this end, I measured GABAergic currents along the post-natal development of these mice and made histological observations of the Purkinje cells linear density. Secondly, I took part of a behavioral study to test the influence of a compound acting on the chloride gradient in two genetic models of autism: Oprm1-/- and Fmr1-/- mice. During my thesis I showed a delay in the development of the chloride gradient. I also observed that a prenatal exposition of sodium valproate induced a post-natal Purkinje cells loss. Finally, the compound I worked with improves the autistic phenotype and opens the perspective for translational potential
2
Fontaine, Charlotte. "Modélisation de la diffusion intermembranaire des ions de chlorure dans un neurone pyramidal hippocampique." Master's thesis, Université Laval, 2007. http://hdl.handle.net/20.500.11794/19544.
Full text
3
Bos, Rémi. "La double personnalité de l'inhibition dans la moelle épinière." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM5070.
Full textAbstract:
Les travaux entrepris au cours de cette thèse ont eu pour but d'étudier la modulation de la transmission synaptique inhibitrice au niveau des réseaux moteurs spinaux, à la fois au cours du développement et après lésion de la moelle épinière. Le nouveau-né présente des activités motrices spontanées qui jouent un rôle important dans la maturation des muscles et des réseaux de neurones de la moelle épinière. Dans une première étude, nous avons identifié l'un des mécanismes impliqués dans la genèse de ces activités chez le rat nouveau-né in vitro. Nous avons démontré que l'activation des récepteurs GABAᴀ au niveau des terminales d'afférences primaires joue un rôle majeur dans le déclenchement et la propagation de ces activités spontanées. Dans une deuxième étude, nous avons testé la robustesse des dépolarisations de nature GABAergique enregistrées in vitro, c'est-à-dire leur dépendance vis-à-vis des paramètres du milieu de perfusion. Nous avons démontré que l'action dépolarisante des neurotransmetteurs GABA/glycine au niveau des motoneurones et celle du GABA au niveau des terminales d'afférences primaires ne sont pas dues à une fourniture énergétique insuffisante. La dernière étude a été consacrée à la modulation de la transmission synaptique inhibitrice après lésion de la moelle épinière. Nous avons montré que l'activation des récepteurs 5-HT2 (R5-HT2), particulièrement celle de l'isoforme 5-HT2ᴀ, renforce le poids synaptique inhibiteur via une hyperpolarisation du potentiel d'équilibre des ions chlorure (ECl) et une augmentation d'expression de KCC2 au niveau de la membrane des motoneuronesThe aim of this thesis was to explore the modulation of the inhibitory synaptic transmission within the spinal motor networks, both during development and after SCI. Spontaneous movements are an ubiquitous feature of fetal and infant behavior. They provide signals that are important for the development of muscles and the assembly of neuronal networks in the spinal cord. In a first study, we characterized one of the mechanisms underlying spontaneous motor behaviors in the in vitro spinal cord preparation isolated from neonatal rats. We demonstrated that the GABA is playing a key role in promoting spontaneous activity through primary afferent depolarizations which reach firing threshold. In the second part of my thesis, we tested the robustness of the in vitro GABAergic depolarizations and their dependence on the aCSF parameters. We demonstrated that during development the depolarizing actions of GABA/glycine on motoneurons and GABA on primary afferent terminals are not due to inadequate energy supply. In the last part of my thesis, we focused on the modulation of the inhibitory synaptic transmission following SCI. We demonstrated that activation of the 5-HT2 receptors, particularly the 5-HT2ᴀ subtype, strengthens inhibitory synaptic transmission to spinal motoneurons by hyperpolarizing the reversal potential of Cl- ions (ECl) and by increasing the cell-membrane expression of KCC2. This phenomenon reduces spasticity after SCI in rats. Upregulation of KCC2 function by targeting 5-HT2ᴀ receptors therefore opens new therapeutic strategies for the treatment of spasticity following SCI
4
Strömberg, Jessica. "Sex and stress steroid modulation of GABA mediated chloride ion flux in rat CNS." Doctoral thesis, Umeå universitet, Obstetrik och gynekologi, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1056.
Full textAbstract:
Background: Sex and stress steroids are metabolized to 3a-hydroxy-pregnane-steroid metabolites such as allopregnanolone (Allo) and tetrahydrodeoxycorticosterone (THDOC). Allo and THDOC are neuroactive steroids that are metabolized in the brain and act in brain as potent positive GABAA receptor function modulators. Allo as well as THDOC levels increase during stress. Allo has been associated with a number of symptoms and malfunctions such as impaired memory function and negative mood symptoms in a subgroup of individuals both for animals and humans. Pregnane steroids with 3b-hydroxy-configuration (3b-steroids) have been shown to reduce the Allo enhanced GABA effect. Aims: The aims for the present thesis were to investigate the effect of 3b-steroids on the GABA mediated GABAA receptor function in presence of positive GABAA receptor modulators. Further, the regional variances between the 3b-steroids as well as the mechanism of the effect were studied. Finally, the effect of stress steroid metabolites on the GABAA receptor function was investigated. Results: 3b-OH-5a-pregnane-20-one reduced the Allo enhanced GABA mediated chloride ion uptake into cortical microsacs. The 3b-isomer reduced the efficacy of Allo without shift the concentration response curve. It is therefore suggested that the 3b-isomer has a non-competitive effect. Further, it was shown that the 3b-isomer reduced the Allo effect in a selective way since the 3b-isomer did not interact with other positive modulators or with GABA itself. Five tested 3b-steroids reduced the Allo enhanced GABA mediated chloride ion uptake in cerebral cortex and hippocampus as well as the Allo prolongation on spontaneous inhibitory postsynaptic currents (sIPSCs) in preoptic nucleus. In cerebellum on the other hand the 3b-steroids showed to have weaker or no effect compared to the other tested regions. Interestingly, in absence of Allo, two of the 3b-steroids positively modulated the GABA stimulated GABAA receptor function. In absence of Allo, 5b-pregnane-3b,20(R)-diol increased the desensitization rate of current response. In contrast to the reducing effect on the Allo induced prolongation on sIPSCs, the effect of the 3b-steroid on GABA application, was not altered in presence of Allo. The mechanism of the 3b-steroid is therefore suggested being desensitization dependent in contrast to Allo, which has been suggested to decrease the GABA unbinding rate. In contrast to the enhanced effect of Allo, glucocorticoid metabolites reduced the GABA mediated chloride ion uptake in a concentration dependent way. The results in present thesis indicate that both sex and stress steroid metabolites interact with the GABAA receptor function. The knowledge that diversity of endogenous steroids interact with the GABAA receptor function is of importance for further understanding of different sex and stress steroid related symptoms and syndromes.
5
Buchin, Anatoly. "Modeling of single cell and network phenomena of the nervous system : ion dynamics during epileptic oscillations and inverse stochastic resonance." Thesis, Paris, Ecole normale supérieure, 2015. http://www.theses.fr/2015ENSU0041/document.
Full textAbstract:
Dans cette thèse nous avons utilisé des méthodes de systèmes dynamiques et des simulations numériques pour étudier les mécanismes d'oscillations d'épilepsie associés à des concentrations d’ions dynamiques et au comportement bimodal des cellules Purkinje du cervelet. Le propos général de ce travail est l'interaction entre les propriétés intrinsèques des neurones simple et la structure d'entrée synaptique contrôlant l'excitabilité neuronale. Dans la première partie de la thèse nous avons développé un modèle de transition de crise épileptique dans le lobe temporal du cerveau. Plus précisément nous nous sommes concentrés sur le rôle du cotransporteur KCC2, qui est responsable de la maintenance du potassium extracellulaire et du chlorure intracellulaire dans les neurones. Des données expérimentales récentes ont montré que cette molécule est absente dans un groupe significatif de cellules pyramidales dans le tissue neuronal de patients épileptiques suggérant son rôle épileptogène. Nous avons trouvé que l'addition d’une quantité critique de cellules pyramidale KCC2 déficient au réseau de subiculum, avec une connectivité réaliste, peut provoquer la génération d’oscillations pathologiques, similaire aux oscillations enregistrées dans des tranches de cerveau épileptogène humaines. Dans la seconde partie de la thèse, nous avons étudié le rôle du bruit synaptique dans les cellules de Purkinje. Nous avons étudié l'effet de l'inhibition de la génération du potentiel d’action provoquée par injection de courant de bruit, un phénomène connu comme résonance stochastique inverse (RSI). Cet effet a déjà été trouvé dans des modèles neuronaux, et nous avons fournis sa première validation expérimentale. Nous avons trouvé que les cellules de Purkinje dans des tranches de cerveau peuvent être efficacement inhibées par des injectionsde bruit de courant. Cet effet est bien reproduit par le modèle phénoménologique adapté pour différentes cellules. En utilisant des méthodes de la théorie de l'information, nous avons montré que RSI prend en charge une transmission efficace de l'information des cellules de Purkinje simples suggérant son rôle pour les calculs du cerveletIn this thesis we used dynamical systems methods and numericalsimulations to study the mechanisms of epileptic oscillations associated with ionconcentration changes and cerebellar Purkinje cell bimodal behavior. The general issue in this work is the interplay between single neuron intrinsicproperties and synaptic input structure controlling the neuronal excitability. In the first part of this thesis we focused on the role of the cellular intrinsicproperties, their control over the cellular excitability and their response to thesynaptic inputs. Specifically we asked the question how the cellular changes ininhibitory synaptic function might lead to the pathological neural activity. We developed a model of seizure initiation in temporal lobe epilepsy. Specifically we focused on the role of KCC2 cotransporter that is responsible for maintaining the baseline extracellular potassium and intracellular chloride levels in neurons. Recent experimental data has shown that this cotransporter is absent in the significant group of pyramidal cells in epileptic patients suggesting its epileptogenic role. We found that addition of the critical amount of KCC2-deficient pyramidal cells to the realistic subiculum network can switch the neural activity from normal to epileptic oscillations qualitatively reproducing the activity recorded in human epileptogenic brain slices. In the second part of this thesis we studied how synaptic noise might control the Purkinje cell excitability. We investigated the effect of spike inhibition caused by noise current injection, so-called inverse stochastic resonance (ISR). This effect has been previously found in single neuron models while we provided its first experimental evidence. We found that Purkinje cells in brain slices could be efficiently inhibited by current noise injections. This effect is well reproduced by the phenomenological model fitted for different cells. Using methods of information theory we showed that ISR supports an efficient information transmission of single Purkinje cells suggesting its role for cerebellar computations
6
Marafiga, Joseane Righes. "Efeito diferencial do diazepam sobre a atividade da enzima Na+,K+-ATPase no hipocampo e córtex entorrinal." Universidade Federal de Santa Maria, 2016. http://repositorio.ufsm.br/handle/1/11848.
Full textAbstract:
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESNa+,K+-ATPase is ubiquitously expressed in the plasma membrane of all animal cells where serves as the principal regulator of intracellular ion homeostasis. Na+,K+-ATPase activity is activated by Na+ and K+ and current evidence indicates that total Na+,K+-ATPase activity is, in general, inhibited by anions. However, the effect of pharmacologically-induced Cl- flux on α1- and α2/3-subunit containing Na+,K+-ATPase activity is not established. In this study we investigated the effect of diazepam, a GABAA receptor positive allosteric modulator, on α1- and α2/3-subunit containing Na+,K+-ATPase activity. Hippocampal and cortical slices were incubated with diazepam (0, 0.05, 0.15 or 0.5 μM) and/or flumazenil (0, 0.005, 0.015, 0.05, 0.15, 0.5 or 1.5 μM) for 10 minutes. After incubation the slices were homogenized and α1 and α2/3 Na+,K+-ATPase activity were assayed using ouabain 3 μM (that inhibits α2/3-subunit containing Na+,K+-ATPase) and 4 mM (that inhibits both isoforms). Diazepam caused a 50% decrease of α2/3-subunit containing Na+,K+-ATPase activity in the hippocampus, but did not alter enzyme activity in the entorhinal cortex. The effect of diazepam was prevented by flumazenil, indicating that the decrease of Na+,K+-ATPase was involved GABAA receptors. Furthermore, a low chloride medium abolished the diazepam-induced decrease of Na+,K+-ATPase activity. Our data suggests that Na+,K+-ATPase in the hippocampus is sensitive to the pharmacological effects of a benzodiazepine by GABAA receptor-mediated mechanisms. Keywords: sodium pump. GABAA receptor. diazepam. flumazenil. chloride ion. hippocampus. entorhinal córtex.
A enzima Na+,K+-ATPase, ou bomba de sódio, é expressa na membrana plasmática de células eucarióticas, onde atua como principal regulador da homeostase iônica intracelular. A enzima Na+,K+-ATPase é ativada pelos íons Na+ and K+ e evidências indicam que a atividade total da enzima Na+,K+-ATPase é inibida por ânions. Entretanto, o efeito do fluxo de cloreto induzido farmacologicamente sobre a atividade das subunidades α1 e α2/3 da enzima Na+,K+-ATPase ainda não foi investigado. Neste estudo, nós investigamos o efeito do diazepam, um modulador alostérico positivo do receptor GABAA na atividade específica das subunidades α1 e α2/3 da Na+,K+-ATPase. Fatias de hipocampo e de córtex entorrinal foram incubadas com diazepam (0; 0,05; 0,15 ou 0,5 μM) e/ou flumazenil (0; 0,005, 0,015; 0,05; 0,15; 0,5 ou 1,5 μM) por 10 minutos. Após a incubação, as fatias foram homogeneizadas e a atividade das subunidades α1 e α2/3 da enzima Na+,K+-ATPase foi determinada. Diazepam diminuiu 50% a atividade da subunidade α2/3 da Na+,K+-ATPase no hipocampo, mas não alterou a atividade da enzima em córtex entorrinal. O efeito do diazepam foi prevenido por flumazenil, indicando que a diminuição da atividade da Na+,K+-ATPase envolveu a ativação dos receptores GABAA. Além disso, a baixa concentração de cloreto no meio de incubação aboliu a diminuição da atividade enzimática induzida por diazepam. Nossos dados sugerem que a enzima Na+,K+-ATPase no hipocampo é sensível a efeitos farmacológicos dos benzodiazepínicos por meio de mecanismos ativados por receptores GABAérgicos.
7
Fontaine, Charlotte. "Modélisation de la diffusion intermembranaire des ions de chlorure dans un neurone pyramidal hippocampique /." 2007. http://www.theses.ulaval.ca/2007/24951/24951.pdf.
Full textBooks on the topic "GABA Ions chlorure"
1
Giovanni, Biggio, Costa Erminio, and Capo Boi Conference on Neuroscience (5th : 1987 : Villasimius, Italy), eds. Chloride channels and their modulation by neurotransmitters and drugs. New York: Raven Press, 1988.
Find full textBook chapters on the topic "GABA Ions chlorure"
1
Olsen, R. W., and M. Gordey. "GABAA Receptor Chloride Ion Channels." In Pharmacology of Ionic Channel Function: Activators and Inhibitors, 499–517. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-642-57083-4_19.
Full text
2
Olsen, R. W., M. Bureau, R. W. Ransom, L. Deng, A. Dilber, G. Smith, M. Krestchatisky, and A. J. Tobin. "The GABA Receptor-Chloride Ion Channel Protein Complex." In Neuroreceptors and Signal Transduction, 1–14. Boston, MA: Springer US, 1988. http://dx.doi.org/10.1007/978-1-4757-5971-6_1.
Full text
3
Morrow, A. Leslie, Pascale Montpied, and Steven M. Paul. "Ethanol and the GABAA Receptor-Gated Chloride Ion Channel." In Neuropharmacology of Ethanol, 49–76. Boston, MA: Birkhäuser Boston, 1991. http://dx.doi.org/10.1007/978-1-4757-1305-3_3.
Full text
4
DARLISON, MARK G. "Molecular Characterization of GABA-Gated Chloride Ion Channels from Complex and Simple Nervous Systems." In Handbook of Membrane Channels, 303–15. Elsevier, 1994. http://dx.doi.org/10.1016/b978-0-12-550640-3.50025-3.
Full textConference papers on the topic "GABA Ions chlorure"
1
Newbound, T. D., A. N. Al-Nasser, M. P. Sang, and W. J. Carrigan. "Recognition and Prevention of Distillate Fuel Emulsions." In ASME Turbo Expo 2006: Power for Land, Sea, and Air. ASMEDC, 2006. http://dx.doi.org/10.1115/gt2006-90030.
Full textAbstract:
This paper describes a case study involving chronic plugging of 5μm particulate filters in a gas turbine diesel fuel system in a Red Sea refinery. Rapid plugging of the filters was caused by water-in-diesel emulsions generated in diesel fuel supply tanks. Sludge with a wax-like appearance recovered from the 5 μm filters was, in fact, found to be composed of up to 50 percent water with no significant wax content. X-ray studies of the filter catch solids revealed a variety of iron oxide phases, sodium chloride, and high concentrations of sodium sulfate. Microbial cultures inoculated from storage tank ‘rag’ layers yielded moderate to high counts of general aerobic bacteria (GAB), moderate fungal cultures (yeast and molds) and low sulfate reducing bacteria (SRB). Elemental analysis of water in supply tanks where microbial activity was highest revealed ion concentrations similar to those found in Red Sea water. Sulfur isotope ratios in sulfate from filter catches suggest that much of the sulfate was derived from microbial metathesis of sulfur-bearing hydrocarbons. Frequent contamination of on-shore liquid hydrocarbon fuel tanks with sea water can cause corrosion and create a favorable environment for bacterial growth. Surfactant byproducts of microbial activity are capable of stabilizing emulsions, suspending water soluble salts such as sodium sulfate, and metals such as lead and copper. Copper is well known to promote gum formation, while all of these contaminants are potentially corrosive to gas turbine hot gas path components.