Department of Anesthesiology

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Prolongation of hippocampal miniature inhibitory postsynaptic currents in mice lacking the GABA(A) receptor alpha1 subunit.

TitleProlongation of hippocampal miniature inhibitory postsynaptic currents in mice lacking the GABA(A) receptor alpha1 subunit.
Publication TypeJournal Article
Year of Publication2002
AuthorsGoldstein PA, Elsen FP, Ying S-W, Ferguson C, Homanics GE, Harrison NL
JournalJ Neurophysiol
Volume88
Issue6
Pagination3208-17
Date Published2002 Dec
ISSN0022-3077
KeywordsAnimals, Electric Conductivity, GABA Agonists, Hippocampus, Interneurons, Mice, Mice, Knockout, Neural Inhibition, Pyramidal Cells, Pyridines, Reaction Time, Receptors, GABA-A, Synaptic Transmission
Abstract

GABA(A) receptors (GABA(A)-Rs) are pentameric structures consisting of two alpha, two beta, and one gamma subunit. The alpha subunit influences agonist efficacy, benzodiazepine pharmacology, and kinetics of activation/deactivation. To investigate the contribution of the alpha1 subunit to native GABA(A)-Rs, we analyzed miniature inhibitory postsynaptic currents (mIPSCs) in CA1 hippocampal pyramidal cells and interneurons from wild-type (WT) and alpha1 subunit knock-out (alpha1 KO) mice. mIPSCs recorded from interneurons and pyramidal cells obtained from alpha1 KO mice were detected less frequently, were smaller in amplitude, and decayed more slowly than mIPSCs recorded in neurons from WT mice. The effect of zolpidem was examined in view of its reported selectivity for receptors containing the alpha1 subunit. In interneurons and pyramidal cells from WT mice, zolpidem significantly increased mIPSC frequency, prolonged mIPSC decay, and increased mIPSC amplitude; those effects were diminished or absent in neurons from alpha1 KO mice. Nonstationary fluctuation analysis of mIPSCs indicated that the zolpidem-induced increase in mIPSC amplitude was associated with an increase in the number of open receptors rather than a change in the unitary conductance of individual channels. These data indicate that the alpha1 subunit is present at synapses on WT interneurons and pyramidal cells, although differences in mIPSC decay times and zolpidem sensitivity suggest that the degree to which the alpha1 subunit is functionally expressed at synapses on CA1 interneurons may be greater than that at synapses on CA1 pyramidal cells.

DOI10.1152/jn.00885.2001
Alternate JournalJ. Neurophysiol.
PubMed ID12466441
Grant ListAA-10422 / AA / NIAAA NIH HHS / United States
GM-45129 / GM / NIGMS NIH HHS / United States
GM-47818 / GM / NIGMS NIH HHS / United States
GM-52035 / GM / NIGMS NIH HHS / United States
GM-62195 / GM / NIGMS NIH HHS / United States