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Inhibitory actions of the gamma‐aminobutyric acid in pediatric Sturge‐Weber syndrome
Author(s) -
Tyzio Roman,
Khalilov Ilgam,
Represa Alfonso,
Crepel Valerie,
Zilberter Yuri,
Rheims Sylvain,
Aniksztejn Laurent,
Cossart Rosa,
Nardou Romain,
Mukhtarov Marat,
Minlebaev Marat,
Epsztein Jérôme,
Milh Mathieu,
Becq Helene,
Jorquera Isabel,
Bulteau Christine,
Fohlen Martine,
Oliver Viviana,
Dulac Olivier,
Dorfmüller Georg,
Delalande Olivier,
BenAri Yehezkel,
Khazipov Roustem
Publication year - 2009
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21711
Subject(s) - neuroscience , inhibitory postsynaptic potential , gabaa receptor , excitatory postsynaptic potential , epileptogenesis , membrane potential , depolarization , patch clamp , glutamate receptor , chemistry , gamma aminobutyric acid , electrophysiology , epilepsy , biology , receptor , endocrinology , biochemistry
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. Interpretation 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. Ann Neurol 2009;66:209–218