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GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons
Benzodiazepines (BDZs) are known to increase the amplitude and duration of IPSCs. Moreover, at low [GABA], BDZs strongly enhance GABAergic currents suggesting the up-regulation of agonist binding while their action on gating remains a matter of debate. In the present study we have examined the impac...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Blackwell Publishing Ltd
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375456/ https://www.ncbi.nlm.nih.gov/pubmed/17855751 http://dx.doi.org/10.1113/jphysiol.2007.143602 |
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author | Mozrzymas, Jerzy W Wójtowicz, Tomasz Piast, Michał Lebida, Katarzyna Wyrembek, Paulina Mercik, Katarzyna |
author_facet | Mozrzymas, Jerzy W Wójtowicz, Tomasz Piast, Michał Lebida, Katarzyna Wyrembek, Paulina Mercik, Katarzyna |
author_sort | Mozrzymas, Jerzy W |
collection | PubMed |
description | Benzodiazepines (BDZs) are known to increase the amplitude and duration of IPSCs. Moreover, at low [GABA], BDZs strongly enhance GABAergic currents suggesting the up-regulation of agonist binding while their action on gating remains a matter of debate. In the present study we have examined the impact of flurazepam and zolpidem on mIPSCs by investigating their effects on GABA(A)R binding and gating and by considering dynamic conditions of synaptic receptor activation. Flurazepam and zolpidem enhanced the amplitude and prolonged decay of mIPSCs. Both compounds strongly enhanced responses to low [GABA] but, surprisingly, decreased the currents evoked by saturating or half-saturating [GABA]. Analysis of current responses to ultrafast GABA applications indicated that these compounds enhanced binding and desensitization of GABA(A) receptors. Flurazepam and zolpidem markedly prolonged deactivation of responses to low [GABA] but had almost no effect on deactivation at saturating or half-saturating [GABA]. Moreover, at low [GABA], flurazepam enhanced desensitization–deactivation coupling but zolpidem did not. Recordings of responses to half-saturating [GABA] applications revealed that appropriate timing of agonist exposure was sufficient to reproduce either a decrease or enhancement of currents by flurazepam or zolpidem. Recordings of currents mediated by recombinant (‘synaptic’) α1β2γ2 receptors reproduced all major findings observed for neuronal GABA(A)Rs. We conclude that an extremely brief agonist transient renders IPSCs particularly sensitive to the up-regulation of agonist binding by BDZs. |
format | Text |
id | pubmed-2375456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-23754562008-11-15 GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons Mozrzymas, Jerzy W Wójtowicz, Tomasz Piast, Michał Lebida, Katarzyna Wyrembek, Paulina Mercik, Katarzyna J Physiol Neuroscience Benzodiazepines (BDZs) are known to increase the amplitude and duration of IPSCs. Moreover, at low [GABA], BDZs strongly enhance GABAergic currents suggesting the up-regulation of agonist binding while their action on gating remains a matter of debate. In the present study we have examined the impact of flurazepam and zolpidem on mIPSCs by investigating their effects on GABA(A)R binding and gating and by considering dynamic conditions of synaptic receptor activation. Flurazepam and zolpidem enhanced the amplitude and prolonged decay of mIPSCs. Both compounds strongly enhanced responses to low [GABA] but, surprisingly, decreased the currents evoked by saturating or half-saturating [GABA]. Analysis of current responses to ultrafast GABA applications indicated that these compounds enhanced binding and desensitization of GABA(A) receptors. Flurazepam and zolpidem markedly prolonged deactivation of responses to low [GABA] but had almost no effect on deactivation at saturating or half-saturating [GABA]. Moreover, at low [GABA], flurazepam enhanced desensitization–deactivation coupling but zolpidem did not. Recordings of responses to half-saturating [GABA] applications revealed that appropriate timing of agonist exposure was sufficient to reproduce either a decrease or enhancement of currents by flurazepam or zolpidem. Recordings of currents mediated by recombinant (‘synaptic’) α1β2γ2 receptors reproduced all major findings observed for neuronal GABA(A)Rs. We conclude that an extremely brief agonist transient renders IPSCs particularly sensitive to the up-regulation of agonist binding by BDZs. Blackwell Publishing Ltd 2007-11-15 2007-09-13 /pmc/articles/PMC2375456/ /pubmed/17855751 http://dx.doi.org/10.1113/jphysiol.2007.143602 Text en © 2007 The Authors. Journal compilation © 2007 The Physiological Society |
spellingShingle | Neuroscience Mozrzymas, Jerzy W Wójtowicz, Tomasz Piast, Michał Lebida, Katarzyna Wyrembek, Paulina Mercik, Katarzyna GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons |
title | GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons |
title_full | GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons |
title_fullStr | GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons |
title_full_unstemmed | GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons |
title_short | GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons |
title_sort | gaba transient sets the susceptibility of mipscs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375456/ https://www.ncbi.nlm.nih.gov/pubmed/17855751 http://dx.doi.org/10.1113/jphysiol.2007.143602 |
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