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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: γ-Aminobutyric acid (GABAa) receptor β3 subunits were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamp. Injected oocytes exhibited an increased resting membrane conductance and more depolarized membrane potentials compared to uninjected control cells. Oocytes expressing β3 subunits were insensitive to GABA and muscimol, but pentobarbitone increased the membrane conductance in a concentration-dependent manner. The membrane current response to pentobarbitone reversed at the Cl−equilibrium potential and at relatively high concentrations (〉500 μM), a rebound CI− current was induced following the removal of pentobarbitone. In transfected human embryonic kidney (HEK) cells, the rebound current amplitude was reduced by desensitizing the β3 receptor with increased durations of ligand application. Both picrotoxin (0.5 nM to 10 μM) and Zn2+ (10 nM to 100 μM) reduced the resting membrane conductance for β3 cDNA-injected oocytes. These oocytes were insensitive to flurazepam (5 μM) and alphaxalone (10 μM), but responded with increased membrane conductance to propofol (10 μM) and pregnanolone (50 nM to 5 μM). The antagonists, bicuculline (10 μM) and strychnine (50 nM to 100 μM), also induced conductance increases in a concentration dependent manner; however, glycine (1 mM) was inactive. It was concluded that β3 subunits form spontaneously opening ion channels that can be up-regulated by some allosteric modulators, principally by pentobarbitone and propofol and, surprisingly, by bicuculline and strychnine, whilst picrotoxin and Zn2+ acted as antagonists. Computer modelling of some kinetic schemes was used to describe the rebound current observed in transfected HEK cells. This indicated that pentobarbitone, after modulation of the conductance, is potentially capable of further binding to the β3 receptor complex ‘driving’ the receptor into one or more desensitized states. This phenomenon may be of some importance for native neuronal GABAA receptors, where pentobarbitone can also evoke rebound current activation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The interaction of zinc with pre- and postsynaptic GABAB receptors was studied in adult rat hippocampal slices using intracellular recording in CA1 and CA3 pyramidal neurons. Zinc (50 – 300 μM) antagonized baclofen responses with a variable potency, whereas CGP-35348 (100 μM) or barium (300 μM) produced a more substantial and consistent inhibition. Zinc also induced giant GABAA-mediated depolarizing potentials (GDP) in these neurons. After blocking GABAA and excitatory synaptic transmission, monosynaptic hyperpolarizing inhibitory postsynaptic potentials (IPSP) mediated by GABAB receptors (IPSPB) were inhibited by CGP-35348 or barium; however, zinc increased the latency and prolonged the duration of the IPSPB and also induced the appearance of spontaneous giant GABAB-mediated hyperpolarizing potentials (GHP). In some cells, IPSPBs in zinc exhibited a multiphasic appearance. The early component was partially inhibited by 300 μM zinc and was followed by a late GHP. CGP-35348 at 100 μM inhibited the early monosynaptic IPSPB but not the GHP; however, at 300 μM both components were blocked. Paired-pulse inhibition of the IPSPB was used to assess the effect of zinc on presynaptic GABAB receptors. Neither the zinc-chelating agent CP94 (400 μM) nor zinc affected this phenomenon. CGP-35348, barium and polyvalent cations, such as cadmium, copper, cobalt, manganese, iron and aluminium, failed to induce giant potentials in hippocampal neurons. It is concluded that zinc is apparently unique in synchronizing the release of GABA to produce GDPs and GHPs.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 349 (1991), S. 521-524 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Intracellular recording from adult rat CA3 hippocampal neurons (P〉 90) revealed mainly spontaneous inhibitory postsynaptic potentials (i.p.s.ps) and occasional action potentials (Fig. la). Bath-application of zinc (50-300 fxM) induced the appearance of large spontaneous depolarizations ...
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 377 (1995), S. 344-348 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Tyrosine phosphorylation of GABAA receptors was analysed in human embryonic kidney cells5 7 (A293; CRL 1573) expressing GABAA-receptor al, |31 and y2L subunits. Receptors composed of these subunits can reproduce many of the properties of neuronal GABAA receptors1 3'5 7. Tagging of the y2L subunit ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 444 (2006), S. 486-489 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Inhibitory neurotransmission mediated by GABAA receptors can be modulated by the endogenous neurosteroids, allopregnanolone and tetrahydro-deoxycorticosterone. Neurosteroids are synthesized de novo in the brain during stress, pregnancyand after ethanol consumption, and disrupted ...
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 427 (1994), S. 481-486 
    ISSN: 1432-2013
    Keywords: Zinc ; Long-term potentiation ; Excitatory amino acid receptors ; Hippocampus ; Intracellular recording ; Zinc chelator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The phenomenon of long-term potentiation is frequently promulgated as an example of learning and memory mechanisms at the synaptic level in the mammalian central nervous system. In the CA3 region of the hippocampus there is an abundance of zinc, which is located in presynaptic mossy fibre nerve terminals. Stimulation of these fibres can cause the release of zinc, which interacts with excitatory amino acid receptors and may therefore modulate long-term potentiation. We now demonstrate in CA1 and CA3 neurons that zinc (100–300 μM) enhances non-N-methyl-d-aspartate-receptor-mediated responses whilst reducing excitatory synaptic transmission and inhibiting long-term potentiation. However, by using zinc-chelating agents, endogenously released zinc following high-frequency stimulation in the stratum lucidum does not appear to have any modulatory role in excitatory synaptic transmission and long-term potentiation. These results indicate that an increase in the level of extracellular zinc can limit excitatory synaptic transmission in the CA1 or CA3 region and further suggests that pathologies that can be related to excessive levels of endogenous zinc may have implications for synaptic plasticity in CA3 neurons.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature genetics 38 (2006), S. 801-806 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) α1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic ...
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