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Blockage of [A.sub.2A] and [A.sub.3] adenosine receptors decreases the desensitization of human [GABA.sub.A] receptors microtransplanted to Xenopus oocytes
- Source :
- Proceedings of the National Academy of Sciences of the United States. Sept 15, 2009, Vol. 106 Issue 37, p15927, 5 p.
- Publication Year :
- 2009
-
Abstract
- We previously found that the endogenous anticonvulsant adenosine, acting through [A.sub.2A] and [A.sub.3] adenosine receptors (ARs), alters the stability of currents ([I.sub.GABA]) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of [I.sub.GABA] 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 GABAA receptors revealed instability, manifested by a large [I.sub.GABA] rundown, which in most of the oocytes ([approximately equal to] 70%) was obviously impaired by the new [A.sub.2A] antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new [A.sub.3] receptor antagonist (ANR235) significantly improved [I.sub.GABA] stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered [I.sub.GABA] rundown on ANR94 treatment. Our findings indicate that antagonizing [A.sub.2A] and [A.sub.3] receptors increases the [I.sub.GABA] stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy. epilepsy | focal cortical dysplasia
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 37
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.208692671