Blockage of A2A and A3 adenosine receptors decreases the desensitization of human GABAA receptors microtransplanted to Xenopus oocytes

Cristina Roseti, Eleonora Palma, Katiuscia Martinello, Sergio Fucile, Roberta Morace, Vincenzo Esposito, Gianpaolo Cantore, Antonietta Arcella, Felice Giangaspero, Eleonora Aronica, Addolorata Mascia, Giancarlo Di Gennaro, Pier Paolo Quarato, Mario Manfredi, Gloria Cristalli, Catia Lambertucci, Gabriella Marucci, Rosaria Volpini, Cristina Limatola, Fabrizio Eusebi

Research output: Contribution to journalArticle

Abstract

We previously found that the endogenous anticonvulsant adenosine, acting through A2A and A3 adenosine receptors (ARs), alters the stability of currents (IGABA) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of IGABA expressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABA A receptors revealed instability, manifested by a large I GABA rundown, which in most of the oocytes (≈70%) was obviously impaired by the new A2A antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A3 receptor antagonist (ANR235) significantly improved IGABA stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered IGABA rundown on ANR94 treatment. Our findings indicate that antagonizing A2A and A3 receptors increases the IGABA stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.

Original languageEnglish
Pages (from-to)15927-15931
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number37
DOIs
Publication statusPublished - Sep 15 2009

Keywords

  • Epilepsy
  • Focal cortical dysplasia

ASJC Scopus subject areas

  • General

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