P2X2 and P2X4 receptor expression is regulated by a GABA(A) receptor-mediated mechanism in the gerbil hippocampus.
Fast responses to extracellular ATP are mediated by the activation of P2X receptors. Native and cloned P2X receptors are permeable to monovalent cations such as Na+ and K+ as well as divalent cations such as Ca2+. However, altered P2X receptor expression has not been definitively determined under pathological conditions, particularly in epilepsy. Here we show that, in the seizure-sensitive (SS) gerbil hippocampus, a recognized genetic epilepsy model, the expressions of both P2X2 and P2X4 receptors are markedly decreased as compared with that in the seizure-resistant (SR) gerbil. These alterations are closely related to changes in gamma-aminobutyric acid (GABA) concentrations induced by vigabatrin (VGB) or 3-mercaptopropionic acid (3-MPA) treatment. Furthermore, the regulation of both P2X receptor expression in the gerbil hippocampus was mediated by the GABA(A) receptor, not GABA(B). These results suggest that the GABA(A) receptor-mediated modulation of P2X receptor expression may play an important role in the regulation of neuronal excitability.
Kang
Tae-Cheon
TC
Department of Anatomy, College of Medicine, Hallym University, Chunchon 200-702, South Korea. tckang@hallym.ac.kr
An
Sung-Jin
SJ
Park
Seung-Kook
SK
Hwang
In-Koo
IK
Won
Moo Ho
MH
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D018682:GABA Agents / Q000494:pharmacology; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; D013045:Species Specificity; D020888:Vigabatrin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018682:GABA Agents; C546401:P2RX2 protein, human; C548226:P2RX4 protein, human; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; D015097:3-Mercaptopropionic Acid; D020888:Vigabatrin