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Proc Natl Acad Sci U S A
2005 Feb 15;1027:2514-8. doi: 10.1073/pnas.0409687102.
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Abnormal GABAA receptors from the human epileptic hippocampal subiculum microtransplanted to Xenopus oocytes.
Palma E
,
Spinelli G
,
Torchia G
,
Martinez-Torres A
,
Ragozzino D
,
Miledi R
,
Eusebi F
.
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We studied the properties of GABAA receptors microtransplanted from the human temporal lobe epilepsy (TLE)-associated brain regions to Xenopus oocytes. Cell membranes, isolated from surgically resected brain specimens of drug-resistant TLE patients, were injected into frog oocytes, which rapidly incorporated human GABAA receptors, and any associated proteins, into their surface membrane. The receptors originating from different epileptic brain regions had a similar run-down but an affinity for GABA that was approximately 60% lower for the subiculum receptors than for receptors issuing from the hippocampus proper or the temporal lobe neocortex. Moreover, GABA currents recorded in oocytes injected with membranes from the subiculum had a more depolarized reversal potential compared with the hippocampus proper or neocortex of the same patients. Quantitative RT-PCR analysis was performed of the GABAA receptor alpha1- to alpha5-, beta1- to beta3-, gamma2- to gamma3-, and delta-subunit mRNAs. The levels of expression of the alpha3-, alpha5-, and beta1- to beta3- subunit mRNAs are significantly higher, with the exception of gamma2-subunit whose expression is lower, in subiculum compared with neocortex specimens. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE subiculum leads to the expression of GABAA receptors with a relatively low affinity. This abnormal behavior of the subiculum GABAA receptors may contribute to epileptogenesis.
Assaf,
Release of endogenous Zn2+ from brain tissue during activity.
, Pubmed
Assaf,
Release of endogenous Zn2+ from brain tissue during activity.
,
Pubmed
Ben-Ari,
Kainate, a double agent that generates seizures: two decades of progress.
2000,
Pubmed
Bothwell,
Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy.
2001,
Pubmed
Brown,
Molecular mechanisms of benzodiazepine-induced down-regulation of GABAA receptor alpha 1 subunit protein in rat cerebellar granule cells.
1996,
Pubmed
Cohen,
On the origin of interictal activity in human temporal lobe epilepsy in vitro.
2002,
Pubmed
Coulter,
Mossy fiber zinc and temporal lobe epilepsy: pathological association with altered "epileptic" gamma-aminobutyric acid A receptors in dentate granule cells.
2000,
Pubmed
Gibbs,
Differential epilepsy-associated alterations in postsynaptic GABA(A) receptor function in dentate granule and CA1 neurons.
1997,
Pubmed
Hosie,
Zinc-mediated inhibition of GABA(A) receptors: discrete binding sites underlie subtype specificity.
2003,
Pubmed
Khalilov,
In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures.
2003,
Pubmed
Köhling,
Neuroscience. GABA becomes exciting.
2002,
Pubmed
Kullmann,
Genetics of epilepsy.
2002,
Pubmed
Kusano,
Cholinergic and catecholaminergic receptors in the Xenopus oocyte membrane.
1982,
Pubmed
,
Xenbase
Loup,
Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy.
2000,
Pubmed
Marsal,
Incorporation of acetylcholine receptors and Cl- channels in Xenopus oocytes injected with Torpedo electroplaque membranes.
1995,
Pubmed
,
Xenbase
Miledi,
Chloride current induced by injection of calcium into Xenopus oocytes.
1984,
Pubmed
,
Xenbase
Miledi,
Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes.
2002,
Pubmed
,
Xenbase
Palma,
Microtransplantation of membranes from cultured cells to Xenopus oocytes: a method to study neurotransmitter receptors embedded in native lipids.
2003,
Pubmed
,
Xenbase
Palma,
Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.
2004,
Pubmed
,
Xenbase
Palma,
Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy.
2002,
Pubmed
,
Xenbase
Stein,
GABA generates excitement.
2003,
Pubmed
Stell,
A tale of timing and transport.
2003,
Pubmed
Vadlamudi,
Genetics of temporal lobe epilepsy.
2003,
Pubmed
Wozny,
Comment on "On the origin of interictal activity in human temporal lobe epilepsy in vitro".
2003,
Pubmed
Zhao,
Reduced expression of gamma-aminobutyric acid type A/benzodiazepine receptor gamma 2 and alpha 5 subunit mRNAs in brain regions of flurazepam-treated rats.
1994,
Pubmed
