• Roman Tyzio, Ilgam Khalilov, Alfonso Represa, Valerie Crepel, Yuri Zilberter, Sylvain Rheims, Laurent Aniksztejn, Rosa Cossart, Romain Nardou, Marat Mukhtarov, Marat Minlebaev, Jérôme Epsztein, Mathieu Milh, Helene Becq, Isabel Jorquera, Christine Bulteau, Martine Fohlen, Viviana Oliver, Olivier Dulac, Georg Dorfmüller, Olivier Delalande, Yehezkel Ben-Ari, and Roustem Khazipov.
• INMED-INSERM U901, Marseille, Paris, France.
• Ann. Neurol. 2009 Aug 1; 66 (2): 209-18.

ObjectiveThe 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.MethodsPatch-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.ResultsNeurons 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.InterpretationSWS 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.

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