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Using patch clamp recording techniques in dentate granule cells (DGCs) isolated from patients undergoing temporal lobectomy for intractable epilepsy, we investigated basic properties of GABAA receptors (GABAARs) and pharmacological sensitivity of GABA-evoked currents to modulation by zinc and benzodiazepines (BZ). Properties of human DGC GABAARs were compared to DGC GABAAR properties in control and epileptic rats. Blockade of GABA evoked currents by zinc was significantly enhanced in epileptic human relative to control rat DGCs. Augmentation of the GABAAR current by the non-subunit selective BZ agonist, clonazepam (CNZ) and by the BZ1 specific agonist, zolpidem (ZOL), were not significantly different in human DGCs relative to control or epileptic rat. GABA potency was significantly higher in epileptic human DGCs than in control or epileptic rat DGCs. The significantly enhanced efficacy of zinc in blocking GABA currents in epileptic human DGCs mirrors that seen in epileptic rat DGCs, and was coupled with mossy fiber sprouting evident in both epileptic human and rat dentate gyrus. The aberrant mossy fibers provide a novel zinc delivery system within the epileptic dentate gyrus. The mossy fiber release of zinc onto DGCs coupled with the enhanced zinc sensitivity of GABAARs in epileptic DGCs, may lead to 'dynamic disinhibition' which could compromise inhibitory efficacy in the epileptic rat and human hippocampus.

Titel:	GABAA receptor function in epileptic human dentate granule cells : Comparison to epileptic and control rat
Autor/in / Beteiligte Person:	SHUMATE, M. D ; LIN, D. D ; GIBBS, J. W ; HOLLOWAY, K. L ; COULTER, D. A
Link:	E-Journal im Bestand der UB Hagen? View record from PASCAL Archive
Quelle:	WONOEP IV: Workshop on the Neurobiology of EpilepsyEpilepsy research 32(1-2):114-128; Jg. 32 (1998) 1-2, S. 114-128
Veröffentlichung:	Amsterdam: Elsevier, 1998
Medientyp:	Konferenz
Umfang:	print, 1 p.1/2
ISSN:	0920-1211 (print)
Schlagwort:	Neurology Neurologie Sciences biologiques et medicales Biological and medical sciences Sciences medicales Medical sciences Système nerveux (sémiologie, syndromes) Nervous system (semeiology, syndromes) Syndromes encéphaliques généraux: céphalées, douleurs de la face, syncopes, épilepsie, hypertension intracrânienne, oedème cérébral. Infirmité motrice cérébrale Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Encéphale pathologie Cerebral disorder Encéfalo patología Epilepsie partielle complexe Complex partial epilepsy Epilepsia parcial compleja Mammalia Rodentia Système nerveux central pathologie Central nervous system disease Sistema nervosio central patología Système nerveux pathologie Nervous system diseases Sistema nervioso patología Vertebrata Agoniste Agonist Agonista Animal Antagoniste Antagonist Antagonista Benzodiazépine dérivé Benzodiazepine derivatives Benzodiazepina derivado Clonazépam Clonazepam Electrodiagnostic Electrodiagnosis Electrodiagnóstico Epilepsie temporale Temporal lobe epilepsy Epilepsia temporal Etude comparative Comparative study Estudio comparativo Hippocampe Hippocampus Hipocampo Homme Human Hombre Méthode patch clamp Patch clamp method Método patch clamp Neurone en grain Granule neuron Neurona en grano Noyau dentelé Dentate nucleus Núcleo dentado Propriété biologique Biological properties Propiedad biológica Rat Rata Récepteur gabaergique A Gabaergic receptor A Receptor gabaminérgico A Réfractaire Refractory Refractario Zinc
Sonstiges:	Nachgewiesen in: PASCAL Archive Sprachen: English Original Material: INIST-CNRS Document Type: Conference Paper File Description: text Language: English Author Affiliations: Department of Physiology, Medical College of Virginia, Richmond, VA 23398-0599, United States ; Department of Pharmacology and Toxicology, Richmond, VA 23398-0599, United States ; Department of Anatomy, Richmond, VA 23398-0599, United States ; Department of Neurosurgery, Richmond, VA 23398-0599, United States ; The MCV Comprehensive Epilepsy Institute of Virginia Commonwealth University, Richmond, VA 23298, United States ; Department of Neurology, Richmond VA 23398-0599, United States Rights: Copyright 1999 INIST-CNRS ; CC BY 4.0 ; Sauf mention contraire ci-dessus, le contenu de cette notice bibliographique peut être utilisé dans le cadre d’une licence CC BY 4.0 Inist-CNRS / Unless otherwise stated above, the content of this bibliographic record may be used under a CC BY 4.0 licence by Inist-CNRS / A menos que se haya señalado antes, el contenido de este registro bibliográfico puede ser utilizado al amparo de una licencia CC BY 4.0 Inist-CNRS Notes: Neurology

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GABAA receptor function in epileptic human dentate granule cells : Comparison to epileptic and control rat