GABA_A Receptors Containing Gamma1 Subunits Contribute to Inhibitory Transmission in the Central Amygdala

Abstract

Esmaeili A, Lynch JW, Sah P. GABA A receptors containing gamma1 subunits contribute to inhibitory transmission in the central amygdale.

GABAA Receptor α and γ Subunits Shape Synaptic Currents via Different Mechanisms

“…Experiments using flunitrazepam and diazepam demonstrate that benzodiazepines are ineffective at enhancing synaptic currents mediated by ␥1-containing GABA A Rs. This result is consistent with whole cell peak current measurements of ␥1-containing GABA A Rs (18), and key differences in the amino acid sequence between ␥2L and ␥1 that have been shown to affect the potency with which benzodiazepine-site ligands modulate currents (49 -52).…”

“…␥1-Containing GABA A Rs Are Insensitive to Benzodiazepine Current Enhancement-Because ␥1-containing receptors have been reported to be less sensitive to benzodiazepine drugs (18,19,21), we compared the actions of flunitrazepam and diazepam on IPSCs from cells expressing either ␣2␤2␥1 or ␣2␤2␥2L receptors. As shown in Fig.…”

“…The ID and TM4 of GABA receptor subunits is crucial for clustering of receptors at post-synaptic sites (12), and our results suggest that, at these engineered synapses, ␥1-and ␥2L-containing GABA A Rs have different synaptic kinetics because of differences in their clustering properties. Thus, at neuronal synapses in situ, it is possible that GABA receptors containing ␥1 and ␥2 subunits may also be differentially targeted (18,53). Subunit-specific clustering mechanisms have already been noted for ␣ subunits in neurons.…”

Impact of infralimbic inputs on intercalated amygdala neurons: A biophysical modeling study

“…For the GABA A synaptic current, t 1 ¼ 0.8 msec, t 2 ¼ 13 msec for ITC cells (Geracitano et al 2007), and t 1 ¼ 0.8 msec, t 2 ¼ 40 msec for Ce neurons (Esmaeili et al 2009). The maximal conductances were chosen as: g AMPA, max ¼ 1 nS, g NMDA, max ¼ 0.5 nS (Li et al 2009), and g GABAA, max ¼ 0.6 nS (Geracitano et al 2007).…”

Optimizing the Expression of Recombinant αβγ GABAA Receptors in HEK293 Cells for High-Throughput Screening

“…This agrees with previous studies that demonstrated that γ subunits confer zinc insensitivity to αβ GABA A Rs. 10,12 To distinguish the pharmacological properties of α1β1γ1 and α1β1γ2 GABA A Rs, we investigated the effects of DMcM and zolpidem, both of which discriminate strongly between γ1-and γ2-containing receptors. DMcM potently inhibits γ2-containing GABA A Rs but has either no effect on or modestly potentiates γ1-containing GABA A Rs.…”