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Competitive GABA(A) receptor antagonists increase the proportion of functional high-affinity alpha 6 subunit-containing receptors in granule cells of adult rat cerebellum
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UNSPECIFIED (2003) Competitive GABA(A) receptor antagonists increase the proportion of functional high-affinity alpha 6 subunit-containing receptors in granule cells of adult rat cerebellum. NEUROPHARMACOLOGY, 44 (1). pp. 56-69. ISSN 0028-3908
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Official URL: http://dx.doi.org/10.1016/S0028-3908(02)00331-3
Abstract
To investigate the properties of alpha6 subunit-containing GABA(A) receptors, whole-cell patch-clamp recordings were made from granule cells in adult rat cerebellar slices. In control, only currents evoked by low concentrations of GABA were significantly reduced in amplitude by furosemide, the alpha6 subunit-containing receptor antagonist. However, in the presence of competitive GABA(A) receptor antagonists, the furosemide block of currents evoked by higher GABA concentrations was markedly increased. Zinc, which preferentially blocks alpha6 subunit-containing receptors, also produced an increased block in the presence of bicuculline. To investigate whether similar effects occurred at synaptic receptors, inhibitory postsynaptic currents (IPSCs) were recorded. In most cells, furosemide produced little or no reduction in evoked IPSC amplitude. However in the presence of SR95531, a competitive antagonist, furosemide markedly reduced IPSC amplitude. One hypothesis, which could account for these observations, is that competitive antagonists prevent the continual activation of alpha6beta2/3gamma2 receptors by endogenous GABA and thus prevent their desensitisation. This hypothesis appears feasible as prolonged applications of low concentrations of GABA to recombinant alpha6beta2gamma2s receptors resulted in their desensitisation. (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: | January 2003 |
| Volume: | 44 |
| Number: | 1 |
| Number of Pages: | 14 |
| Page Range: | pp. 56-69 |
| Publication Status: | Published |
| URI: | http://wrap.warwick.ac.uk/id/eprint/10001 |
Data sourced from Thomson Reuters' Web of Knowledge
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