NDLI: GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

Content Provider	PubMed Central
Author	Palma, Eleonora Cristina, Roseti Francesca, Maiolino Fucile, Sergio Martinello, Katiuscia Mazzuferi, Manuela Aronica, Eleonora Manfredi, Mario Esposito, Vincenzo Cantore, Gianpaolo Miledi, Ricardo Michele, Simonato Eusebi, Fabrizio
Copyright Year	2007
Abstract	A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (I GABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, I GABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease.
Related Links	http://dx.doi.org/10.1073/pnas.0710522105
Starting Page	20944
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	52
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-12-26
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

$GABA_{A}-current$ rundown of temporal lobe epilepsy is associated with repetitive activation of $GABA_{A}$ “phasic” receptors

Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy

Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy.

Dissecting the Molecular Determinants of $GABA_{A}$ Receptors Current Rundown, a Hallmark of Refractory Human Epilepsy

Enhancement of GABAA-current run-down in the hippocampus occurs at the first spontaneous seizure in a model of temporal lobe epilepsy

Pharmacological plasticity of GABAA receptors at dentate gyrus synapses in a rat model of temporal lobe epilepsy

Correction: Loss of Resting-State Posterior Cingulate Flexibility Is Associated with Memory Disturbance in Left Temporal Lobe Epilepsy

Apoptosis through Death Receptors in Temporal Lobe Epilepsy-Associated Hippocampal Sclerosis

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

Similar Documents

$GABA_{A}-current$ rundown of temporal lobe epilepsy is associated with repetitive activation of $GABA_{A}$ “phasic” receptors

Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy

Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy.

Dissecting the Molecular Determinants of $GABA_{A}$ Receptors Current Rundown, a Hallmark of Refractory Human Epilepsy

Enhancement of GABAA-current run-down in the hippocampus occurs at the first spontaneous seizure in a model of temporal lobe epilepsy

Pharmacological plasticity of GABAA receptors at dentate gyrus synapses in a rat model of temporal lobe epilepsy

Correction: Loss of Resting-State Posterior Cingulate Flexibility Is Associated with Memory Disturbance in Left Temporal Lobe Epilepsy

Apoptosis through Death Receptors in Temporal Lobe Epilepsy-Associated Hippocampal Sclerosis

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors