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  • 1
    ISSN: 1432-1106
    Keywords: Calcium ; Hippocampal slice ; CA1 ; ω-Agatoxin IVA ; ω-Conotoxin GVIA ; ω-Conotoxin ; MVIIC ; Nimodipine ; Ethosuximide ; Trimethadion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The contribution of T-, L-, N-, P-, and Q-type Ca2+ channels to pre-and postsynaptic Ca2+ entry during stimulus-induced high neuronal activity in area CA1 of rat hippocampal slices was investigated by measuring the effect of specific blockers on stimulus-induced decreases in extracellular Ca2+ concentration ([Ca2+]0). [Ca2+]0 was measured with ion-selective electrodes in stratum radiatum (SR) and stratum pyramidale (SP), while Ca2+ entry into neurons was induced with stimulus trains (20 Hz for 10 s) alternately delivered to SR and the alveus, respectively. The [Ca2+]0 decreases recorded in SR in response to SR stimulation represented mainly presynaptic Ca2+ entry (Capre), while [Ca2+]0 decreases recorded in SP in response to alvear stimulation were predominantly based on postsynaptic Ca2+ entry (Capost). Ethosuximide and trimethadione were ineffective m concentrations up to 1 mM. At 10 mM, they reduced Capost and, much less, also Capre Nimodipine (25 μM) reduced Capost and, to a minor extent, Capre. ω-Agatoxin IVA (0.4–1 μM) and ω-conotoxin MVIIC (1 μM) also reduced both Capre and Capost, but with a stronger action on Capre. ω-Conotoxin GVIA (3–8 μM) reduced Capost without effect on Capre. We conclude that during stimulus-induced, high-frequency neuronal activity Capost is carried by P/Q-, N-, and L-type channels and probably a further channel type different from these channels. Capre includes at least P/Q-and possibly L-type channels. N-type channels did not contribute to Capre in our experiments. Since ethosuximide and trimethadione were only effective in high concentrations, their action may be unspecific. Thus, T-type channels do not seem to play a major part in Ca2+ entry in this situation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 97 (1993), S. 209-224 
    ISSN: 1432-1106
    Keywords: Hypoxia ; Neocortical slice ; Synaptic transmission ; GABAergic inhibition ; Interneurons ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To analyze the functional consequences of hypoxia on the efficacy of intracortical inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), extra- and intracellular recordings were obtained from rat primary somatosensory cortex in vitro. Hypoxia, induced by transient N2 aeration, caused a decrease in stimulus-evoked inhibitory postsynaptic potentials (IPSPs), followed by a pronounced anoxic depolarization. Upon reoxygenation, the fast (f-) and long-latency (l-) IPSP showed a positive shift in the reversal potential by 24.4 and 14.9 mV, respectively. The peak conductance of the f-and l-IPSP was reversibly reduced in the postanoxic period by 72% and 94%, respectively. Extracellular field potential recordings and application of a paired-pulse inhibition protocol confirmed the enhanced sensitivity of inhibitory synaptic transmission for transient oxygen deprivation. Intracellular recordings from morphologically or electrophysiologically identified interneurons did not reveal any enhanced susceptibility for hypoxia as compared to pyramidal cells, suggesting that inhibitory neurons are not selectively impaired in their functional properties. Intracellularly recorded spontaneous IPSPs were transiently augmented in the postanoxic period, indicating that presynaptic GABA release was not suppressed. Developmental studies in adult (older than postnatal day 28), juvenile (P14–18), and young (P5-8) neocortical slices revealed a prominent functional resistance of immature tissue for hypoxia. In comparison with adult cortex, the hypoxia-induced reduction in excitatory and inhibitory synaptic transmission was significantly smaller in immature cortex. Our data indicate a hypoxia-induced distinct reduction of postsynaptic GABAergic mechanisms, leading to the manifestation of intracortical hyperexcitability as a possible functional consequence.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 78 (1989), S. 233-242 
    ISSN: 1432-1106
    Keywords: Hoppocampus ; Granule cells ; Long lasting inhibition ; Frequency habituation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In paired pulse stimulation experiments the mechanism underlying frequency habituation of postsynaptic potentials in dentate granule cells of rat hippocampal slices was studied by measuring extra and intracellular potentials as well as changes in extracellular calcium ([Ca2+]0) and potassium concentrations ([K+]0). Orthodromic stimulation of the perforant path induced in most granule cells a late, slow hyperpolarization (SH), lasting for up to 1.2 s. During the SH the membrane conductance was increased by up to 40%. The reversal potential of the SH was around -90 mV and varied with the [K+]0. Frequency habituation was seen in all cells with the SH, whereas cells which display frequency potentiation had no SH. Lowering of [Ca2+]0 reversed paired pulse induced frequency habituation into frequency potentiation at [Ca2+]0 levels where the SH disappeared. Phaclofen blocked the SH and reversed frequency habituation into frequency potentiation. Elevating [Mg2+]0 also reversed frequency habituation into frequency potentiation and reduced the SH. We conclude that the SH represents a late, slow IPSP which is responsible for frequency habituation in dentate granule cells. We noted that during repetitive stimulation the SH soon started to fade. This effect can in part be attributed to extracellular K+-accumulation as suggested by the K+-dependence of the slow IPSP and the observations of changes in [K+]0 during repetitive stimulation. This could explain why frequency habituation reverses into frequency potentiation during repetitive stimulation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1106
    Keywords: Extracellular Na+ concentration ; Quisqualate (quis) ; N-methyl-D-aspartate (NMDA) ; Tetrodotoxin (TTX) ; Hippocampal area CA1 ; Rat ; Extracellular Ca2+ concentration ; Extracellular Mg2+ concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Decreases in extracellular sodium concentration ([Na+]o) and associated slow negative field potentials (fp's) were monitored with double barreled sodium sensitive/reference microelectrodes in area CA1 of rat hippocampal slices during iontophoretic application of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and quisqualate (quis). The effects of lowering [Ca2+]o on these signals were compared to those of lowering [Mg2+]o. Both NMDA- and quis-induced decreases in [Na+]o of up to 60 mM and in the fp's of up to 8 mV. Decreasing [Mg2+]o enhanced NMDA-induced signals, whereas quis-induced signals were unaffected. Lowering [Ca2+]o also enhanced NMDA signals, although somewhat less than lowering [Mg2+]o. This effect was still present, even when voltage dependent Na+ currents were blocked by 10-7 tetrodotoxin. Interestingly, quis-induced signals could be enhanced in a low Ca2+ medium as well, but only when high quis concentrations were used. The results suggest that, during the sorts of large decreases of [Ca2+]o observed during seizure activity, activation of NMDA receptors is facilitated.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1912
    Keywords: Entorhinal cortex ; Isomers ; Low magnesium epilepsy ; Losigamone ; Maximal electroshock test ; Mice ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Losigamone (AO-33) is a recemate of a tetronic acid derivative. The effects of losigamone and its three isomers (AO-242, AO-294 and AO-23) were compared on maximal electroshock (MES) induced convulsions in mice and on different patterns of extracellularly recorded, low Mg 2+ induced epileptiform activity in slices of the rat temporal cortex. Lowering Mg 2+ induced recurrent short discharges in areas CA3 and CA1 while ictaform events that lasted for many seconds were induced in the entorhinal cortex. In the hippocampus the activity stayed stable over a number of hours. In contrast, the ictaform events in the entorhinal cortex changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. Afterdischarges and interictal events were absent. 50 μM AO-242 showed a similar efficacy to 50 μM AO-33 in reducing and blocking epileptiform discharges in areas CA1 and CA3 while 50 μM AO-294 and 50 μM AO-23 had weaker effects than 50 μM AO-33. Concentrations of 50 μM and 100 μM AO-242 showed a similar efficacy to AO-33 on ictaform events in the entorhinal cortex. Late recurrent discharges were also blocked by AO-33 and AO-242 although at higher concentrations (300 μM). The in vitro observations are with respect to order of efficacy in accordance with the in vivo data obtained in the maximal electroshock test in mice. The order of potency in the MES test was AO-242〉AO-33≫AO-294≫ AO-23. The results show that the erythro-isomer AO-23, although active, is much less potent than AO-33. Of the two optical isomers of losigamone the (+) isomer AO-242 is more active than the (−) form AO-294.
    Type of Medium: Electronic Resource
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