| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Psychopathologie et Pharmacologie de la cognition, INSERM U405, Strasbourg, France2 Neurophysiologie Cellulaire et Intégrée, ULP/CNRS UMR 7519, Strasbourg, France
In the lithium–pilocarpine model (Li-pilocarpine) of temporal lobe epilepsy, GABAA receptor-mediated inhibitory postsynaptic currents (GABAA IPSCs) were recorded in dentate gyrus granule cells (GCs) from adult rat hippocampal slices. The properties of GABAA IPSCs were compared before and after superfusion of modulators in control conditions (Li-saline rats) and in Li-pilocarpine rats 24–48 h and 3–5 months (epileptic rats) after status epilepticus (SE). The mean peak amplitude of GABAA IPSCs increased by about 40% over Li-saline values in GCs 24–48 h after SE and remained higher in epileptic rats. In Li-pilocarpine rats, studied at 24–48 h after SE, diazepam (1 µM) lost 65% of its effectiveness at increasing the half-decay time (T50%) of GABAA miniature IPSCs (mIPSCs). Diazepam had no effects on mIPSC T50% in epileptic rats. The benzodiazepine ligand flumazenil (1 µM), acting as an antagonist in Li-saline rats, exhibited a potent inverse agonistic effect on GABAA mIPSCs of GCs from Li-pilocarpine rats 24–48 h and 3–5 months after SE. The neurosteroid allopregnanolone (100 nM), which considerably prolonged GABAA mIPSCs in Li-saline rats, totally lost its effect in rats studied 24–48 h after SE. However, this decrease in effectiveness was transient and was totally restored in epileptic rats. In addition to the up-regulation in the number of receptors at individual GC synapses, we propose that these ‘epileptic’ GABAA receptors possess benzodiazepine binding sites with altered allosteric properties. The failure of benzodiazepine and neurosteroid to potentiate inhibition early after SE may be a critical factor in the development of epileptogenesis and occurrence of seizures.
(Received 5 December 2003;
accepted after revision 18 March 2004;
first published online 19 March 2004)
Corresponding author A. Nehlig: INSERM U405, Faculty of Medicine, 11, rue Humann, 67085 Strasbourg, France. Email: nehlig{at}neurochem.u-strasbg.fr
This article has been cited by other articles:
|
|
 |
|
  P. Inquimbert, J.-L. Rodeau, and R. Schlichter Regional Differences in the Decay Kinetics of GABAA Receptor-Mediated Miniature IPSCs in the Dorsal Horn of the Rat Spinal Cord Are Determined by Mitochondrial Transport of Cholesterol J. Neurosci., March 26, 2008; 28(13): 3427 - 3437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Feng, G. C. Mathews, C. Kao, and R. L. Macdonald Alterations of GABAA-Receptor Function and Allosteric Modulation During Development of Status Epilepticus J Neurophysiol, March 1, 2008; 99(3): 1285 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sun, Z. Mtchedlishvili, A. Erisir, and J. Kapur Diminished Neurosteroid Sensitivity of Synaptic Inhibition and Altered Location of the {alpha}4 Subunit of GABAA Receptors in an Animal Model of Epilepsy J. Neurosci., November 14, 2007; 27(46): 12641 - 12650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Payne, W. M. Connelly, J. H. Ives, R. Lehner, B. Furtmuller, W. Sieghart, P. Tiwari, J. M. Lucocq, G. Lees, and C. L. Thompson GABAA {alpha}6-Containing Receptors Are Selectively Compromised in Cerebellar Granule Cells of the Ataxic Mouse, Stargazer J. Biol. Chem., October 5, 2007; 282(40): 29130 - 29143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-s. Qi, J. Yao, C. Fang, B. Luscher, and G. Chen Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal cultures J. Physiol., December 1, 2006; 577(2): 579 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Payne, P. S. Donoghue, W. M. K. Connelly, S. Hinterreiter, P. Tiwari, J. H. Ives, V. Hann, W. Sieghart, G. Lees, and C. L. Thompson Aberrant GABAA Receptor Expression in the Dentate Gyrus of the Epileptic Mutant Mouse Stargazer. J. Neurosci., August 15, 2006; 26(33): 8600 - 8608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schwabe, C. Gavrilovici, D. C. McIntyre, and M. O. Poulter Neurosteroids Exhibit Differential Effects on mIPSCs Recorded From Normal and Seizure Prone Rats J Neurophysiol, September 1, 2005; 94(3): 2171 - 2181. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
