Synaptic GABAA receptor clustering without the γ2 subunit
| Autor: | Mark D. Eyre, Zoltan Nusser, Katalin Kerti-Szigeti |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Flurazepam GABA Agents Protein subunit Green Fluorescent Proteins Convulsants Mice Transgenic Neocortex Biology In Vitro Techniques Membrane Potentials Synapse Mice Postsynaptic potential medicine Animals Patch clamp Receptor Desoxycorticosterone Neurons GABAA receptor General Neuroscience Lysine Articles Receptors GABA-A Electric Stimulation Cell biology medicine.anatomical_structure Anti-Anxiety Agents Inhibitory Postsynaptic Potentials Synapses Female Neuroscience medicine.drug Carbolines |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 34(31) |
| ISSN: | 1529-2401 |
| Popis: | Rapid activation of postsynaptic GABAA receptors (GABAARs) is crucial in many neuronal functions, including the synchronization of neuronal ensembles and controlling the precise timing of action potentials. Although the γ2 subunit is believed to be essential for the postsynaptic clustering of GABAARs, synaptic currents have been detected in neurons obtained from γ2(-/-) mice. To determine the role of the γ2 subunit in synaptic GABAAR enrichment, we performed a spatially and temporally controlled γ2 subunit deletion by injecting Cre-expressing viral vectors into the neocortex of GABAARγ2(77I)lox mice. Whole-cell recordings revealed the presence of miniature IPSCs in Cre(+) layer 2/3 pyramidal cells (PCs) with unchanged amplitudes and rise times, but significantly prolonged decays. Such slowly decaying currents could be evoked in PCs by action potentials in presynaptic fast-spiking interneurons. Freeze-fracture replica immunogold labeling revealed the presence of the α1 and β3 subunits in perisomatic synapses of cells that lack the γ2 subunit. Miniature IPSCs in Cre(+) PCs were insensitive to low concentrations of flurazepam, providing a pharmacological confirmation of the lack of the γ2 subunit. Receptors assembled from only αβ subunits were unlikely because Zn(2+) did not block the synaptic currents. Pharmacological experiments indicated that the αβγ3 receptor, rather than the αβδ, αβε, or αβγ1 receptors, was responsible for the slowly decaying IPSCs. Our data demonstrate the presence of IPSCs and the synaptic enrichment of the α1 and β3 subunits and suggest that the γ3 subunit is the most likely candidate for clustering GABAARs at synapses in the absence of the γ2 subunit. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|