Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain:
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 frequenc...
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| Format: | Elektronisch E-Book |
| Sprache: | English |
| Veröffentlicht: |
Paris
OECD Publishing
2019
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| Schriftenreihe: | OECD Series on Adverse Outcome Pathways
no.11 |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Zusammenfassung: | 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. |
| Beschreibung: | 1 Online-Ressource (57 p.) |
| DOI: | 10.1787/9226875e-en |
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| indexdate | 2024-11-26T14:55:55Z |
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| spelling | Gong, Ping VerfasserIn aut Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain Ping, Gong and Edward J., Perkins Paris OECD Publishing 2019 1 Online-Ressource (57 p.) Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier OECD Series on Adverse Outcome Pathways no.11 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. Environment Social Issues/Migration/Health Perkins, Edward J... MitwirkendeR ctb FWS01 ZDB-13-SOC FWS_PDA_SOC https://doi.org/10.1787/9226875e-en Volltext |
| spellingShingle | Gong, Ping Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain Environment Social Issues/Migration/Health |
| title | Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain |
| title_auth | Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain |
| title_exact_search | Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain |
| title_full | Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain Ping, Gong and Edward J., Perkins |
| title_fullStr | Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain Ping, Gong and Edward J., Perkins |
| title_full_unstemmed | Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain Ping, Gong and Edward J., Perkins |
| title_short | Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain |
| title_sort | adverse outcome pathway on binding to the picrotoxin site of ionotropic gaba receptors leading to epileptic seizures in adult brain |
| topic | Environment Social Issues/Migration/Health |
| topic_facet | Environment Social Issues/Migration/Health |
| url | https://doi.org/10.1787/9226875e-en |
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