TY - JOUR T1 - GABA<sub>A</sub> Receptor γ2 Subunit Mutations Linked to Human Epileptic Syndromes Differentially Affect Phasic and Tonic Inhibition JF - The Journal of Neuroscience JO - J. Neurosci. SP - 14108 LP - 14116 DO - 10.1523/JNEUROSCI.2618-07.2007 VL - 27 IS - 51 AU - Emmanuel Eugène AU - Christel Depienne AU - Stéphanie Baulac AU - Michel Baulac AU - Jean Marc Fritschy AU - Eric Le Guern AU - Richard Miles AU - Jean Christophe Poncer Y1 - 2007/12/19 UR - http://www.jneurosci.org/content/27/51/14108.abstract N2 - GABA acts on GABAA receptors to evoke both phasic inhibitory synaptic events and persistent, tonic currents. The γ2 subunit of the GABAA receptor is involved in both phasic and tonic signaling in the hippocampus. Several mutations of this subunit are linked to human epileptic syndromes with febrile seizures, yet it is not clear how they perturb neuronal activity. Here, we examined the expression and functional impact of recombinant γ2 in hippocampal neurons. We show that the K289M mutation has no effect on membrane trafficking and synaptic aggregation of recombinant γ2, but accelerates the decay of synaptic currents. In contrast, the R43Q mutation primarily reduces surface expression of recombinant γ2. However, it has no dominant effect on synaptic currents but instead reduces tonic GABA currents, at least in part by reducing surface expression of the α5 subunit. Our data suggests that the phenotypic specificity of mutations affecting the GABAA receptor γ2 gene may result from different actions specific to distinct modes of GABAergic signaling. ER -