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220928 ||| eng |
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|a Gong, Ping
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|a Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
|h Elektronische Ressource
|c Ping, Gong and Edward J., Perkins
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| 260 |
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|a Paris
|b OECD Publishing
|c 2019
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| 300 |
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|a 57 p
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| 653 |
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|a Social Issues/Migration/Health
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| 653 |
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|a Environment
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| 700 |
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|a Perkins, Edward J.
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|a eng
|2 ISO 639-2
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| 989 |
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|b OECD
|a OECD Books and Papers
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|a OECD Series on Adverse Outcome Pathways
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| 028 |
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|a 10.1787/9226875e-en
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| 856 |
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|a oecd-ilibrary.org
|u https://doi.org/10.1787/9226875e-en
|x Verlag
|3 Volltext
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|a 363
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|a 304
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|a 610
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|a This AOP begins with the interaction of chemicals to the picrotoxin binding site of the ionotropic GABA receptor complex causing blockage of the ion channel. As a result, decrease in inward chloride conductance occurs, followed by a reduction in postsynaptic inhibition, reflected as reduced frequency and amplitude of spontaneous inhibitory postsynaptic current or abolishment of GABA-induced firing action. Consequently, the resistance of excitatory neurons to fire is decreased, resulting in the generation of a large excitatory postsynaptic potential (EPSP) that causes voltage-gated Na+ to open, which results in action potentials. The depolarisation is followed by a period of hyper-polarisation mediated by Ca2+-dependent K+ channels or GABA-activated Cl− influx, which becomes smaller, gradually disappears, and is replaced by a depolarisation known as "paroxysmal depolarizing shift" (PDS). A PDS is an indication of epilepsy at the cellular level and initiates the adverse outcome at the organismal level of epileptic seizure
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