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Inhibitory transmission in locus coeruleus neurons expressing GABAA receptor epsilon subunit has a number of unique properties.
J Neurophysiol. 2009 Oct; 102(4):2312-25.JN

Abstract

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.

Authors+Show Affiliations

University Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche, Bordeaux, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19625540

Citation

Belujon, P, et al. "Inhibitory Transmission in Locus Coeruleus Neurons Expressing GABAA Receptor Epsilon Subunit Has a Number of Unique Properties." Journal of Neurophysiology, vol. 102, no. 4, 2009, pp. 2312-25.
Belujon P, Baufreton J, Grandoso L, et al. Inhibitory transmission in locus coeruleus neurons expressing GABAA receptor epsilon subunit has a number of unique properties. J Neurophysiol. 2009;102(4):2312-25.
Belujon, P., Baufreton, J., Grandoso, L., Boué-Grabot, E., Batten, T. F., Ugedo, L., Garret, M., & Taupignon, A. I. (2009). Inhibitory transmission in locus coeruleus neurons expressing GABAA receptor epsilon subunit has a number of unique properties. Journal of Neurophysiology, 102(4), 2312-25. https://doi.org/10.1152/jn.00227.2009
Belujon P, et al. Inhibitory Transmission in Locus Coeruleus Neurons Expressing GABAA Receptor Epsilon Subunit Has a Number of Unique Properties. J Neurophysiol. 2009;102(4):2312-25. PubMed PMID: 19625540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory transmission in locus coeruleus neurons expressing GABAA receptor epsilon subunit has a number of unique properties. AU - Belujon,P, AU - Baufreton,J, AU - Grandoso,L, AU - Boué-Grabot,E, AU - Batten,T F C, AU - Ugedo,L, AU - Garret,M, AU - Taupignon,A I, Y1 - 2009/07/22/ PY - 2009/7/24/entrez PY - 2009/7/25/pubmed PY - 2010/1/21/medline SP - 2312 EP - 25 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 102 IS - 4 N2 - 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. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/19625540/Inhibitory_transmission_in_locus_coeruleus_neurons_expressing_GABAA_receptor_epsilon_subunit_has_a_number_of_unique_properties_ L2 - http://journals.physiology.org/doi/full/10.1152/jn.00227.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -