title: Electrophysiological properties and subunit composition of GABAA receptors in patients with gelastic seizures and hypothalamic hamartoma.
abstract: Abnormalities in GABA(A) receptor structure and/or function have been associated with various forms of epilepsy in both humans and animals. Whether this is true for patients with gelastic seizures and hypothalamic hamartoma (HH) is unknown. In this study, we characterized the pharmacological properties and native subunit composition of GABA(A) receptors on acutely dissociated single neurons from surgically resected HH tissues using patch-clamp, immunocytochemical, and RT-PCR techniques. We found that 1) GABA induced an inward current (I(GABA)) at a holding potential of -60 mV; 2) I(GABA) was mimicked by the GABA(A) receptor agonist muscimol and blocked by the GABA(A) receptor antagonist bicuculline, suggesting that I(GABA) was mediated principally through the GABA(A) receptor; 3) the EC(50) and Hill coefficient derived from the I(GABA) concentration-response curve were 6.8 muM and 1.9, respectively; 4) the current-voltage curve was linear at a reversal potential close to zero; and 5) I(GABA) exhibited low sensitivity to zinc and diazepam but higher sensitivity to pentobarbital and pregnanolone. Additionally, using Xenopus oocytes microtransplanted with normal human hypothalamic tissue, we confirmed that the functional properties of GABA(A) receptors were similar to those seen in small isolated HH neurons. Finally, the expression profile of GABA(A) receptor subunits obtained from normal control human hypothalamic tissue was identical to that from surgically resected human HH tissue. Taken together, our data indicate that GABA(A) receptors on small HH neurons exhibit normal pharmacosensitivity and subunit composition. These findings bear relevance to a broader understanding of inhibitory neurotransmission in human HH tissue.
authors.affiliation: Neurophysiology Lab, Div of Neurology, Barrow Neurological Inst, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA. Jie.Wu@chw.edu
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chang
authors.forename: Guohui
authors.initials: G
authors.lastname: Li
authors.forename: Fenqin
authors.initials: F
authors.lastname: Xue
authors.forename: Jamie
authors.initials: J
authors.lastname: DeChon
authors.forename: Kevin
authors.initials: K
authors.lastname: Ellsworth
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Kechun
authors.initials: K
authors.lastname: Yang
authors.forename: Nasim
authors.initials: N
authors.lastname: Bahadroani
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.forename: Jianliang
authors.initials: J
authors.lastname: Zhang
authors.forename: Harold
authors.initials: H
authors.lastname: Rekate
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.forename: John F
authors.initials: JF
authors.lastname: Kerrigan
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004828:Epilepsies, Partial / Q000150:complications / Q000473:pathology*; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D006222:Hamartoma / Q000150:complications / Q000473:pathology*; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018682:GABA Agents; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid