title: Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome.
abstract: OBJECTIVE
  The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies.
  
  
  METHODS
  Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery.
  
  
  RESULTS
  Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many cells spontaneously fired action potentials at a rate proportional to the level of neuronal depolarization. The reversal potential for GABA-activated currents, assessed by cell-attached single channel recordings, was close to the resting membrane potential. All spontaneously firing neurons recorded in cell-attached mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous epileptiform activity in the form of recurrent population bursts was suppressed by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had little effect on epileptiform activity.
  
  
  CONCLUSIONS
  SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex.
authors.affiliation: INMED-INSERM U901, Marseille, Paris, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Tyzio
authors.forename: Ilgam
authors.initials: I
authors.lastname: Khalilov
authors.forename: Alfonso
authors.initials: A
authors.lastname: Represa
authors.forename: Valerie
authors.initials: V
authors.lastname: Crepel
authors.forename: Yuri
authors.initials: Y
authors.lastname: Zilberter
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rheims
authors.forename: Laurent
authors.initials: L
authors.lastname: Aniksztejn
authors.forename: Rosa
authors.initials: R
authors.lastname: Cossart
authors.forename: Romain
authors.initials: R
authors.lastname: Nardou
authors.forename: Marat
authors.initials: M
authors.lastname: Mukhtarov
authors.forename: Marat
authors.initials: M
authors.lastname: Minlebaev
authors.forename: Jérôme
authors.initials: J
authors.lastname: Epsztein
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
authors.forename: Helene
authors.initials: H
authors.lastname: Becq
authors.forename: Isabel
authors.initials: I
authors.lastname: Jorquera
authors.forename: Christine
authors.initials: C
authors.lastname: Bulteau
authors.forename: Martine
authors.initials: M
authors.lastname: Fohlen
authors.forename: Viviana
authors.initials: V
authors.lastname: Oliver
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Georg
authors.initials: G
authors.lastname: Dorfmüller
authors.forename: Olivier
authors.initials: O
authors.lastname: Delalande
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: Roustem
authors.initials: R
authors.lastname: Khazipov
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D002034:Bumetanide / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D003975:Diazepam / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007539:Isonicotinic Acids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D064506:Solute Carrier Family 12, Member 2; D013341:Sturge-Weber Syndrome / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D007539:Isonicotinic Acids; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; C578877:SLC12A2 protein, human; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; C015300:isoguvacine