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J Neurophysiol (December 1, 2002). 10.1152/jn.00885.2001
Submitted on 29 October 2001
Accepted on 9 August 2002
1 Subunit
1C. V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College, Cornell University, New York, New York 10021; and 2Department of Anesthesiology and 3Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Goldstein, Peter A.,
Frank P. Elsen,
Shui-Wang Ying,
Carolyn Ferguson,
Gregg E. Homanics, and
Neil
L. Harrison.
Prolongation of Hippocampal Miniature Inhibitory Postsynaptic
Currents in Mice Lacking the GABAA Receptor 1 Subunit. J. Neurophysiol. 88: 3208-3217, 2002. GABAA receptors (GABAA-Rs) are
pentameric structures consisting of two 
, two 
, and one 
subunit. The subunit influences agonist efficacy, benzodiazepine
pharmacology, and kinetics of activation/deactivation. To investigate
the contribution of the 1 subunit to native GABAA-Rs, we
analyzed miniature inhibitory postsynaptic currents (mIPSCs) in CA1
hippocampal pyramidal cells and interneurons from wild-type (WT) and
1 subunit knock-out (1 KO) mice. mIPSCs recorded from
interneurons and pyramidal cells obtained from 1 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 1 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 1 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 1
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 1 subunit is functionally expressed at synapses on CA1 interneurons may be greater than that at
synapses on CA1 pyramidal cells.
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