Modulation of synaptic GABAA receptor function by benzodiazepines in area CA3 of rat hippocampal slice cultures - PubMed (original) (raw)
Modulation of synaptic GABAA receptor function by benzodiazepines in area CA3 of rat hippocampal slice cultures
J C Poncer et al. Neuropharmacology. 1996.
Abstract
The effects of the benzodiazepine agonist midazolam on GABAA receptor-mediated inhibition were investigated in area CA3 of hippocampal slice cultures. Midazolam (100 nM) increased the decay time constant (tau OFF) of miniature inhibitory postsynaptic currents (mIPSCs) recorded from pyramidal cells by approximately 40%, but did not significantly affect their activation rate or amplitude, consistent with saturation of postsynaptic GABAA receptors by a quantum of GABA. Non-stationary variance analysis of mIPSCs revealed that the unitary conductance of synaptic GABAA channels (approximately 31 pS) was unaffected by midazolam. Midazolam increased not only the tau OFF (51%), but also the amplitude (23%) of unitary IPSPs, recorded from pairs of monosynaptically connected inhibitory and pyramidal cells. Simulation of unitary IPSPs indicated that the increased amplitude was primarily due to the slow time constant of pyramidal cells. Finally, the mean amplitude, tau OFF, and single-channel conductance of mIPSCs recorded in cultures chronically exposed to midazolam (0.1-10 microM) for 2 weeks were not different from control mIPSCs, nor was their response to midazolam. We conclude that benzodiazepines increase synaptic GABAA channel open time, as described previously, and that this results in an increase in both the amplitude and duration of IPSPs in pyramidal cells.
Similar articles
- Benzodiazepine tolerance at GABAergic synapses on hippocampal CA1 pyramidal cells.
Zeng XJ, Tietz EI. Zeng XJ, et al. Synapse. 1999 Mar 15;31(4):263-77. doi: 10.1002/(SICI)1098-2396(19990315)31:4<263::AID-SYN4>3.0.CO;2-J. Synapse. 1999. PMID: 10051107 - Comparison of midazolam effects on inhibitory postsynaptic currents in hippocampal CA3 with those in CA1.
Kobayashi S, Fujito Y, Matsuyama K, Aoki M. Kobayashi S, et al. Neuroreport. 2005 Jun 21;16(9):1003-7. doi: 10.1097/00001756-200506210-00024. Neuroreport. 2005. PMID: 15931077 - Developmental study of benzodiazepine effects on monosynaptic GABAA-mediated IPSPs of rat hippocampal neurons.
Rovira C, Ben-Ari Y. Rovira C, et al. J Neurophysiol. 1993 Sep;70(3):1076-85. doi: 10.1152/jn.1993.70.3.1076. J Neurophysiol. 1993. PMID: 7901345 - Oestrogen effects in olivo-cerebellar and hippocampal circuits.
Smith SS, Hsu FC, Li X, Frye CA, Faber DS, Markowitz RS. Smith SS, et al. Novartis Found Symp. 2000;230:155-68; discussion 168-72. doi: 10.1002/0470870818.ch12. Novartis Found Symp. 2000. PMID: 10965507 Review. - Insights into the Roles of Midazolam in Cancer Therapy.
Jiao J, Wang Y, Sun X, Jiang X. Jiao J, et al. Evid Based Complement Alternat Med. 2017;2017:3826506. doi: 10.1155/2017/3826506. Epub 2017 Jun 19. Evid Based Complement Alternat Med. 2017. PMID: 28706559 Free PMC article. Review.
Cited by
- Neural bases for addictive properties of benzodiazepines.
Tan KR, Brown M, Labouèbe G, Yvon C, Creton C, Fritschy JM, Rudolph U, Lüscher C. Tan KR, et al. Nature. 2010 Feb 11;463(7282):769-74. doi: 10.1038/nature08758. Nature. 2010. PMID: 20148031 Free PMC article. - Dentate granule cell GABA(A) receptors in epileptic hippocampus: enhanced synaptic efficacy and altered pharmacology.
Cohen AS, Lin DD, Quirk GL, Coulter DA. Cohen AS, et al. Eur J Neurosci. 2003 Apr;17(8):1607-16. doi: 10.1046/j.1460-9568.2003.02597.x. Eur J Neurosci. 2003. PMID: 12752378 Free PMC article. - Status epilepticus increases the intracellular accumulation of GABAA receptors.
Goodkin HP, Yeh JL, Kapur J. Goodkin HP, et al. J Neurosci. 2005 Jun 8;25(23):5511-20. doi: 10.1523/JNEUROSCI.0900-05.2005. J Neurosci. 2005. PMID: 15944379 Free PMC article. - Benzodiazepine treatment induces subtype-specific changes in GABA(A) receptor trafficking and decreases synaptic inhibition.
Jacob TC, Michels G, Silayeva L, Haydon J, Succol F, Moss SJ. Jacob TC, et al. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18595-600. doi: 10.1073/pnas.1204994109. Epub 2012 Oct 22. Proc Natl Acad Sci U S A. 2012. PMID: 23091016 Free PMC article. - Quantal currents at single-site central synapses.
Auger C, Marty A. Auger C, et al. J Physiol. 2000 Jul 1;526 Pt 1(Pt 1):3-11. doi: 10.1111/j.1469-7793.2000.t01-3-00003.x. J Physiol. 2000. PMID: 10878094 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Miscellaneous