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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 632 (1991), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mefenamic acid (MFA) has anti-convulsant and pro-convulsant effects in vivo, and has been shown to potentiate and inhibit GABAA (γ-aminobutyric acid) receptors in vitro. In this study, whole-cell currents were recorded from Xenopus oocytes and human embryonic kidney (HEK) cells expressing human recombinant GABAA receptors to resolve the molecular mechanisms by which MFA modulates GABAA receptor function. We demonstrate that MFA potentiated GABA-activated currents for α1β2 γ2S (EC50 = 3.2 ± 0.5 μm), but not for α1β1 γ2S receptors. MFA also enhanced GABA-activated responses and directly activated α1β2/β3 GABAA receptors, but inhibited responses to GABA on α1β1 constructs (IC50 = 40 ± 7.2 μm). A comparison of β1, β2 and β3 subunits suggested that the positive modulatory action of MFA involved asparagine (N) 290 in the second transmembrane domain (TM2) of the β2 and β3 subunits. Mutation of N290 to serine (S) markedly reduced modulation by MFA in α1β2(N290S)γ2S receptors, whereas α1β1(S290N)γ2S constructs revealed potentiated responses to GABA (EC50 = 7.8 ± 1.7 μm) and direct activation by MFA. The potentiation by MFA displayed voltage sensitivity. The direct activation, potentiation and inhibitory aspects of MFA action were predominantly conferred by the β subunits as the spontaneously active homomeric β1 and β3 receptors were susceptible to modulation by MFA. Molecular comparisons of MFA, loreclezole and etomidate, agents which exhibit similar selectivity for GABAA receptors, revealed their ability to adopt similar structural conformations. This study indicates that N290 in TM2 of β2 and β3 subunits is important for the regulation of GABAA receptor function by MFA. Our data provide a potential molecular mechanism for the complex central effects of MFA in vivo.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Developmental Biology 138 (1990), S. 313-323 
    ISSN: 0012-1606
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 284 (1980), S. 560-561 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The experiments were done on the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles of the rat, and on human intercostal muscle obtained during thoracic surgery. The isolated muscles were mounted in a bath perfused with oxygenated mammalian Ringer10, which contained ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 280 (1979), S. 326-328 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Experiments were carried out on the cutaneous pectoris muscle of Rana temporria, stretched to a striation spacing of about 3.6 ?? to reduce contraction. The bathing solution contained (in mM): NaCl, 120; KC1,2; 0,1.8 or 12 CaCl2. In the 0 Ca2+ solution, 1 mM EGTA and 5 mM MgCl2 were added; pH was ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 279 (1979), S. 638-639 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Experiments were carried out on the frog (Rana temporria] sartorius muscle, at a temperature of 5-6 C. The muscle was strongly stretched to reduce contraction and its associated artefacts. The normal bathing solution contained (in mM); NaCl, 120; KC1, 2; CaCl2,1.8; HEPES, 4 (pH 7.2). Calcium ...
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 277 (1979), S. 236-238 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Human intercostal nerve-muscle obtained from myasthenia gravis and control patients was dissected in sterile conditions to give small bundles of fibres (-100). Fibre bundles were pinned through their tendons and mounted, under slight tension, on Sylgard frames. They were maintained in Trowell's T-8 ...
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 271 (1978), S. 74-75 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Intercostal muscle from myasthenic and control patients were dissected to give a small bundle of muscle fibres, sometimes with its nerve supply. Stimulation of the nerve was via a glass capillary suction electrode. Preparations were perfused with an oxygenated medium and examined using conventional ...
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 308 (1984), S. 421-424 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Sodium channels and receptors to serotonin and kainate were ‘transplanted’ from human brain into frog oocytes, by isolating messenger RNA from a fetal brain, and injecting it into Xenopus laevis oocytes. The mRNA was translated by the oocyte and induced the appearance of functional ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 412 (1988), S. 22-28 
    ISSN: 1432-2013
    Keywords: Schwann-cell ; Denervation ; End-plate current ; Acetylcholine-receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract End-plates in denervated frog sartorius muscles were investigated, under voltage clamp, to determine the characteristics of miniature endplate currents (mepc) caused by the release of acetylcholine (ACh)-quanta from Schwanncells. Staining for acetylcholinesterase ascertained that in most cases Schwann-cell mepc had been recorded focally from the end-plate. The mean amplitude of Schwann-cell mepc (about 1 nA) was smaller than the amplitude (3–4 nA) of normal nerve evoked mepc. The amplitude distribution of Schwann-cell mepc was skewed, as were also the distributions of decay time constants and of rise times. Some Schwann-cell mepc appeared to be of composite nature, as shown by an inflexion on either the rising or falling phase. The decay time constant τ of both fast and slowly decaying Schwann-cell mepc increased with membrane hyperpolarization suggesting an exponential correlation. The potential dependence was 118±37 mV (means±SD from 6 experiments) for ane-fold change of τ, which does not differ significantly from that for neural mepc (98 mV). The cholinesterase inhibitor neostigmine increased the amplitude and prolonged the time course of Schwann-cell mepc to a similar degree after short and long term denervation, which indicates that cholinesterase was still functional after 3–4 months of denervation. The results show that the characteristics of Schwann-cell mepc resemble in many respects those of neural mepc but are more variable in shape and amplitude.
    Type of Medium: Electronic Resource
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