In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 37 ( 2009-09-15), p. 15927-15931
Abstract:
We previously found that the endogenous anticonvulsant adenosine, acting through A 2A and A 3 adenosine receptors (ARs), alters the stability of currents (I GABA ) generated by GABA A receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of I 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 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 A 2A antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A 3 receptor antagonist (ANR235) significantly improved I GABA stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered I GABA rundown on ANR94 treatment. Our findings indicate that antagonizing A 2A and A 3 receptors increases the I GABA stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0907324106
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2009
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12