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Key Event Title
Reduction, Neuronal synaptic inhibition
|Level of Biological Organization|
Key Event Components
|chemical synaptic transmission||decreased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Blocking iGABA receptor ion channel leading to seizures||KeyEvent||Cataia Ives (send email)||Open for citation & comment||WPHA/WNT Endorsed|
Key Event Description
A reduction in GABA-mediated inhibition of neuronal synaptic signaling is reflected as decreased frequency and amplitude of iGABAR-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) or abolishment of GABA-induced firing action (Newland and Cull-Candy 1992).
How It Is Measured or Detected
Juarez et al. (2013) used primary cultured neurons obtained from the guinea-pig small intestine to detect picrotoxin concentration-dependent (and reversible) inhibition of GABA-induced membrane currents. Williams et al. (2011) used whole-cell in vitro recordings in the rat basolateral amygdala (BLA) to detect the reduced frequency and amplitude of GABAA receptor mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and the amplitude of GABA-evoked postsynaptic currents, both of which were induced by RDX.
Domain of Applicability
See Juarez et al. (2013) for supporting evidence for Guinea pig. For rat, whole-cell in vitro recordings in the rat basolateral amygdala (BLA) showed that RDX reduces the frequency and amplitude of GABAA receptor mediated sIPSCs and the amplitude of GABA-evoked postsynaptic currents, whereas in extracellular field recordings from the BLA, RDX induced prolonged, seizure-like neuronal discharges (Williams et al, 2011).
Newland C F, Cull-Candy S G. On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat. J Physiol 1992; 447: 191–213.
Juarez E H, Ochoa-Cortes F, Miranda-Morales M, Espinosa-Luna R, Montano L M, Barajas-Lopez C. Selectivity of antagonists for the Cys-loop native receptors for ACh, 5-HT and GABA in guinea-pig myenteric neurons. Auton Autacoid Pharmacol 2013; 34(1-2):1-8.
Williams L R, Aroniadou-Anderjaska V, Qashu F, Finne H, Pidoplichko V, Bannon D I et al. RDX binds to the GABA(A) receptor-convulsant site and blocks GABA(A) receptor-mediated currents in the amygdala: a mechanism for RDX-induced seizures. Environ Health Perspect 2011; 119(3):357-363.