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Potentiation of gamma-aminobutyric acid type A receptor-mediated synaptic currents by pentobarbital and diazepam in immature hippocampal CA1 neurons.
J Pharmacol Exp Ther. 1993 Sep; 266(3):1227-35.JP

Abstract

Previous studies have demonstrated age-dependent changes in the expression of gamma-aminobutyric acid type A (GABAA) benzodiazepine receptor binding sites and mRNAs encoding GABAA receptor subunits during postnatal development. However, little is known about the pharmacology of GABAA-mediated synaptic events in immature brain neurons. The effects of pentobarbital and diazepam were examined on the GABAA-mediated inhibitory postsynaptic current (IPSC) in postnatal 2- to 8-day-old (PN 2-8) and 18- to 30-day-old (PN 18-30) hippocampal CA1 neurons, using whole-cell recordings in brain slices. In both age groups of immature neurons recorded with an internal solution containing 2 mM ATP, application of diazepam at a concentration as low as 10 nM consistently potentiated the IPSC and Cl- currents evoked by local ejection of GABA (GABA currents). Pretreatment with the benzodiazepine antagonist, flumazenil, blocked the diazepam-induced potentiation of the IPSC, which suggested a direct action of diazepam on the GABAA/benzodiazepine receptor complex. With a patch pipette solution containing no added ATP, similar application of diazepam caused consistent potentiation of the IPSC in PN 18-30 neurons but not in PN 2-8 neurons. In contrast, pentobarbital potentiated the IPSCs with or without internally applied ATP in the neurons of both age groups. The authors suggest that functional GABAA/benzodiazepine receptors are expressed in neonatal CA1 hippocampal neurons. However, their sensitivity to benzodiazepines is altered by intracellular ATP.

Authors+Show Affiliations

Toronto Hospital Research Institute, Department of Physiology, University of Toronto, Ontario, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8396629

Citation

Zhang, L, et al. "Potentiation of Gamma-aminobutyric Acid Type a Receptor-mediated Synaptic Currents By Pentobarbital and Diazepam in Immature Hippocampal CA1 Neurons." The Journal of Pharmacology and Experimental Therapeutics, vol. 266, no. 3, 1993, pp. 1227-35.
Zhang L, Weiner JL, Carlen PL. Potentiation of gamma-aminobutyric acid type A receptor-mediated synaptic currents by pentobarbital and diazepam in immature hippocampal CA1 neurons. J Pharmacol Exp Ther. 1993;266(3):1227-35.
Zhang, L., Weiner, J. L., & Carlen, P. L. (1993). Potentiation of gamma-aminobutyric acid type A receptor-mediated synaptic currents by pentobarbital and diazepam in immature hippocampal CA1 neurons. The Journal of Pharmacology and Experimental Therapeutics, 266(3), 1227-35.
Zhang L, Weiner JL, Carlen PL. Potentiation of Gamma-aminobutyric Acid Type a Receptor-mediated Synaptic Currents By Pentobarbital and Diazepam in Immature Hippocampal CA1 Neurons. J Pharmacol Exp Ther. 1993;266(3):1227-35. PubMed PMID: 8396629.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiation of gamma-aminobutyric acid type A receptor-mediated synaptic currents by pentobarbital and diazepam in immature hippocampal CA1 neurons. AU - Zhang,L, AU - Weiner,J L, AU - Carlen,P L, PY - 1993/9/1/pubmed PY - 1993/9/1/medline PY - 1993/9/1/entrez SP - 1227 EP - 35 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 266 IS - 3 N2 - Previous studies have demonstrated age-dependent changes in the expression of gamma-aminobutyric acid type A (GABAA) benzodiazepine receptor binding sites and mRNAs encoding GABAA receptor subunits during postnatal development. However, little is known about the pharmacology of GABAA-mediated synaptic events in immature brain neurons. The effects of pentobarbital and diazepam were examined on the GABAA-mediated inhibitory postsynaptic current (IPSC) in postnatal 2- to 8-day-old (PN 2-8) and 18- to 30-day-old (PN 18-30) hippocampal CA1 neurons, using whole-cell recordings in brain slices. In both age groups of immature neurons recorded with an internal solution containing 2 mM ATP, application of diazepam at a concentration as low as 10 nM consistently potentiated the IPSC and Cl- currents evoked by local ejection of GABA (GABA currents). Pretreatment with the benzodiazepine antagonist, flumazenil, blocked the diazepam-induced potentiation of the IPSC, which suggested a direct action of diazepam on the GABAA/benzodiazepine receptor complex. With a patch pipette solution containing no added ATP, similar application of diazepam caused consistent potentiation of the IPSC in PN 18-30 neurons but not in PN 2-8 neurons. In contrast, pentobarbital potentiated the IPSCs with or without internally applied ATP in the neurons of both age groups. The authors suggest that functional GABAA/benzodiazepine receptors are expressed in neonatal CA1 hippocampal neurons. However, their sensitivity to benzodiazepines is altered by intracellular ATP. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8396629/Potentiation_of_gamma_aminobutyric_acid_type_A_receptor_mediated_synaptic_currents_by_pentobarbital_and_diazepam_in_immature_hippocampal_CA1_neurons_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8396629 DB - PRIME DP - Unbound Medicine ER -