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Alterations of GABA A-receptor function and allosteric modulation during development of status epilepticus.
J Neurophysiol. 2008 Mar; 99(3):1285-93.JN

Abstract

Partial limbic seizures in rodents induced by pilocarpine progress from stages I-II (mouth and facial movements; head nodding) to stage III (forelimb clonus) and then progress rapidly to stages IV-V (generalized limbic seizures; rearing, and rearing with falling) followed by status epilepticus (SE). Although limbic seizures in rodents are terminated by benzodiazepines, a group of gamma-aminobutyric acid type A (GABA(A))-receptor positive modulators, significant pharmacoresistance to benzodiazepines develops within minutes during SE. The alterations of GABA(A)-receptor function and allosteric modulation during development of SE are poorly understood. We induced seizures in juvenile rats by administration of lithium followed by pilocarpine, and whole cell recordings of miniature inhibitory postsynaptic currents (mIPSCs) were obtained from hippocampal dentate granule cells in brain slices. Compared with a sham-treated group, mIPSC amplitude was reduced and decay was accelerated at onset of the first occurrence of stage III (S3) seizures [S3(0)], resulting in a reduction in the total charge transfer at S3(0). Recovery of mIPSC amplitude and prolongation of mIPSC decay occurred 30 min after onset of S3 seizures [S3(30)]. The mIPSC frequency was not altered for S3(0) and S3(30) neurons compared with sham neurons. The net enhancement of total charge transfer by diazepam was smaller for S3(30) than that for sham and S3(0) neurons; however, the net reduction of total charge transfer by zinc was greater for S3(30) than that for sham and S3(0) neurons. These findings suggest that substantial plastic changes of GABA(A)-receptor function and allosteric modulation occur rapidly in neurons from juvenile animals during development of SE.

Authors+Show Affiliations

Department of Neurology, Vanderbilt University Medical Center, 465 21st Avenue South, Nashville, TN 37232-8552, USA. huajun.feng@vanderbilt.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18216225

Citation

Feng, Hua-Jun, et al. "Alterations of GABA A-receptor Function and Allosteric Modulation During Development of Status Epilepticus." Journal of Neurophysiology, vol. 99, no. 3, 2008, pp. 1285-93.
Feng HJ, Mathews GC, Kao C, et al. Alterations of GABA A-receptor function and allosteric modulation during development of status epilepticus. J Neurophysiol. 2008;99(3):1285-93.
Feng, H. J., Mathews, G. C., Kao, C., & Macdonald, R. L. (2008). Alterations of GABA A-receptor function and allosteric modulation during development of status epilepticus. Journal of Neurophysiology, 99(3), 1285-93. https://doi.org/10.1152/jn.01180.2007
Feng HJ, et al. Alterations of GABA A-receptor Function and Allosteric Modulation During Development of Status Epilepticus. J Neurophysiol. 2008;99(3):1285-93. PubMed PMID: 18216225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alterations of GABA A-receptor function and allosteric modulation during development of status epilepticus. AU - Feng,Hua-Jun, AU - Mathews,Gregory C, AU - Kao,Chris, AU - Macdonald,Robert L, Y1 - 2008/01/23/ PY - 2008/1/25/pubmed PY - 2008/6/13/medline PY - 2008/1/25/entrez SP - 1285 EP - 93 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 99 IS - 3 N2 - Partial limbic seizures in rodents induced by pilocarpine progress from stages I-II (mouth and facial movements; head nodding) to stage III (forelimb clonus) and then progress rapidly to stages IV-V (generalized limbic seizures; rearing, and rearing with falling) followed by status epilepticus (SE). Although limbic seizures in rodents are terminated by benzodiazepines, a group of gamma-aminobutyric acid type A (GABA(A))-receptor positive modulators, significant pharmacoresistance to benzodiazepines develops within minutes during SE. The alterations of GABA(A)-receptor function and allosteric modulation during development of SE are poorly understood. We induced seizures in juvenile rats by administration of lithium followed by pilocarpine, and whole cell recordings of miniature inhibitory postsynaptic currents (mIPSCs) were obtained from hippocampal dentate granule cells in brain slices. Compared with a sham-treated group, mIPSC amplitude was reduced and decay was accelerated at onset of the first occurrence of stage III (S3) seizures [S3(0)], resulting in a reduction in the total charge transfer at S3(0). Recovery of mIPSC amplitude and prolongation of mIPSC decay occurred 30 min after onset of S3 seizures [S3(30)]. The mIPSC frequency was not altered for S3(0) and S3(30) neurons compared with sham neurons. The net enhancement of total charge transfer by diazepam was smaller for S3(30) than that for sham and S3(0) neurons; however, the net reduction of total charge transfer by zinc was greater for S3(30) than that for sham and S3(0) neurons. These findings suggest that substantial plastic changes of GABA(A)-receptor function and allosteric modulation occur rapidly in neurons from juvenile animals during development of SE. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/18216225/Alterations_of_GABA_A_receptor_function_and_allosteric_modulation_during_development_of_status_epilepticus_ L2 - http://www.physiology.org/doi/full/10.1152/jn.01180.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -