期刊
PLOS ONE
卷 6, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0016911
关键词
-
资金
- Italian Ministero Universita Ricerca [Nu 20072BTSR2_002]
- Compagnia di San Paolo
- University of Genoa [ALCOTRA 2007-2013]
Background: Although converging evidence has suggested that nicotinic acetylcholine receptors (nAChR) play a role in the modulation of GABA release in rat hippocampus, the specific involvement of different nAChR subtypes at presynaptic level is still a matter of debate. In the present work we investigated, using selective alpha 7 and alpha 4 beta 2 nAChR agonists, the presence of different nAChR subtypes on hippocampal GABA nerve endings to assess to what extent and through which mechanisms they stimulate endogenous GABA release. Methodology/Findings: All agonists elicited GABA overflow. Choline (Ch)-evoked GABA overflow was dependent to external Ca2+, but unaltered in the presence of Cd2+, tetrodotoxin (TTX), dihydro-b-erythroidine (DH beta E) and 1-(4,4-Diphenyl-3- butenyl)-3-piperidinecarboxylic acid hydrochloride SKF 89976A. The effect of Ch was blocked by methyllycaconitine (MLA), alpha-bungarotoxin (alpha-BTX), dantrolene, thapsigargin and xestospongin C, suggesting that GABA release might be triggered by Ca2+ entry into synaptosomes through the alpha 7 nAChR channel with the involvement of calcium from intracellular stores. Additionally, 5-Iodo-A-85380 dihydrochloride (5IA85380) elicited GABA overflow, which was Ca2+ dependent, blocked by Cd2+, and significantly inhibited by TTX and DH beta E, but unaffected by MLA, SKF 89976A, thapsigargin and xestospongin C and dantrolene. These findings confirm the involvement of alpha 4 beta 2 nAChR in 5IA85380-induced GABA release that seems to occur following membrane depolarization and opening calcium channels. Conclusions/Significance: Rat hippocampal synaptosomes possess both alpha 7 and alpha 4 beta 2 nAChR subtypes, which can modulate GABA release via two distinct mechanisms of action. The finding that GABA release evoked by the mixture of sub-maximal concentration of 5IA85380 plus sub-threshold concentrations of Ch was significantly larger than that elicited by the sum of the effects of the two agonists is compatible with the possibility that they coexist on the same nerve terminals. These findings would provide the basis for possible selective pharmacological strategies to treat neuronal disorders that involve the dysfunction of hippocampal cholinergic system.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据