Inhibitory transmission in locus coeruleus neurons expressing GABA a receptor epsilon subunit has a number of unique properties
Journal of Neurophysiology. 2009-10-01; 102(4): 2312-2325
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1. J Neurophysiol. 2009 Oct;102(4):2312-25. doi: 10.1152/jn.00227.2009. Epub 2009
Inhibitory transmission in locus coeruleus neurons expressing GABAA receptor
epsilon subunit has a number of unique properties.
Belujon P(1), Baufreton J, Grandoso L, Boué-Grabot E, Batten TF, Ugedo L, Garret
M, Taupignon AI.
(1)University Bordeaux, Centre National de la Recherche Scientifique Unité Mixte
de Recherche, Bordeaux, France.
Fast inhibitory synaptic transmission in the brain relies on ionotropic GABA(A)
receptors (GABA(A)R). Eighteen genes code for GABA(A)R subunits, but little is
known about the epsilon subunit. Our aim was to identify the synaptic
transmission properties displayed by native receptors incorporating epsilon.
Immunogold localization detected epsilon at synaptic sites on locus coeruleus
(LC) neurons. In situ hybridization revealed prominent signals from epsilon, and
mRNAs, some low beta1 and beta3 signals, and no gamma signal. Using in vivo
extracellular and in vitro patch-clamp recordings in LC, we established that
neuron firing rates, GABA-activated currents, and mIPSC charge were insensitive
to the benzodiazepine flunitrazepam (FLU), in agreement with the characteristics
of recombinant receptors including an epsilon subunit. Surprisingly, LC provided
binding sites for benzodiazepines, and GABA-induced currents were potentiated by
diazepam (DZP) in the micromolar range. A number of GABA(A)R ligands
significantly potentiated GABA-induced currents, and zinc ions were only active
at concentrations above 1 muM, further indicating that receptors were not
composed of only alpha and beta subunits, but included an epsilon subunit. In
contrast to recombinant receptors including an epsilon subunit, GABA(A)R in LC
showed no agonist-independent opening. Finally, we determined that mIPSCs, as
well as ensemble currents induced by ultra-fast GABA application, exhibited
surprisingly slow rise times. Our work thus defines the signature of native
GABA(A)R with a subunit composition including epsilon: differential sensitivity
to FLU and DZP and slow rise time of currents. We further propose that alpha(3,)
beta(1/3,) and epsilon subunits compose GABA(A)R in LC.
PMID: 19625540 [Indexed for MEDLINE]