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This Article Full Text Full Text (PDF) All Versions of this Article: 585/1/29    most recent jphysiol.2007.143602v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mozrzymas, J. W. Articles by Mercik, K. Search for Related Content PubMed PubMed Citation Articles by Mozrzymas, J. W. Articles by Mercik, K. Related Collections Neuroscience

Jerzy W. Mozrzymas¹, Tomasz Wójtowicz¹, Micha Piast¹, Katarzyna Lebida¹, Paulina Wyrembek¹ and Katarzyna Mercik¹

¹ Laboratory of Neuroscience, Department of Biophysics, Wrocaw Medical University, Chaubiskiego 3, 50-368 Wroclaw, Poland

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_AR 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’) 1β22 receptors reproduced all major findings observed for neuronal GABA_ARs. We conclude that an extremely brief agonist transient renders IPSCs particularly sensitive to the up-regulation of agonist binding by BDZs.

(Received 21 August 2007; accepted after revision 11 September 2007; first published online 13 September 2007)
Corresponding author T. Wójtowicz: Laboratory of Neuroscience, Department of Biophysics, Wrocaw Medical University, Chaubiñskiego 3, 50-368 Wroclaw, Poland. Email: twojtow{at}biofiz.am.wroc.pl