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Furosemide reveals heterogeneous GABA(A) receptor expression at adult rat Golgi cell to granule cell synapses

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UNSPECIFIED (2002) Furosemide reveals heterogeneous GABA(A) receptor expression at adult rat Golgi cell to granule cell synapses. NEUROPHARMACOLOGY, 43 (4). pp. 737-749. ISSN 0028-3908

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Abstract

The contribution that alpha6 subunit-containing GABA(A) receptors make to inhibitory synaptic transmission to granule cells was investigated by making whole-cell patch clamp recordings from granule cells in adult rat cerebellar slices and applying furosemide, the specific alpha6 subunit-containing GABA(A) receptor antagonist. Endogenous, extracellular GABA continually activated GABA(A) receptors producing a tonic current. Since this current was markedly reduced by furosemide it was probably produced by alpha6 subunit-containing receptors. In contrast, furosemide had little effect on the amplitude or kinetics of fast spontaneous inhibitory postsynaptic currents (sIPSCs), although such sIPSCs were abolished by bicuculline and SR95331. However, the amplitude of evoked EPSCs with a very slow rise and decay were markedly reduced by furosemide. These IPSCs probably resulted from the spillover of GABA from neighbouring synapses activating high affinity alpha6 subunit-containing receptors. In the rest of the cells (40 out of 46), evoked IPSCs had rise and decay kinetics that lay in-between fast sIPSCs and slow 'spillover' IPSCs. Such IPSCs had variable kinetics and also exhibited considerable variation in the magnitude of furosemide block. Thus the GABA, receptors present at adult Golgi cell-granule cell synapses, at a developmental stage where receptor expression is complete, are highly heterogeneous. (C) 2002 Elsevier Science Ltd. All rights reserved.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RS Pharmacy and materia medica
Journal or Publication Title: NEUROPHARMACOLOGY
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
ISSN: 0028-3908
Date: September 2002
Volume: 43
Number: 4
Number of Pages: 13
Page Range: pp. 737-749
Publication Status: Published
URI: http://wrap.warwick.ac.uk/id/eprint/10458

Data sourced from Thomson Reuters' Web of Knowledge

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