神经损伤与功能重建2009，Vol.4Issue(1)：48-59,12.
CB1 Cannabinoid Receptor-Dependent and -Independent Inhibition of Depolarization-Induced Calcium Influx in Oiigodendrocytes
CB1 Cannabinoid Receptor-Dependent and -Independent Inhibition of Depolarization-Induced Calcium Influx in Oiigodendrocytes
摘要
Abstract
Regulation of Ca2+ homeostasis plays a critical role in oligodendrocyte function and survival. Canna-binoid CB2 and CB2 receptors have been shown to regulate Ca2+ levels and/or K+ currents in a variety of cell types. In this study we investigated the effect of cannabinoid compounds on the Ca2+ influx elicited in cultured oligodendro-cytes by transient membrane depolarization with an elevated extracellular K+ concentration (50 mM). The CB2 re-ceptor agonist arachidonoyl-chloro-ethanolamide (ACEA) elicited a concentration-dependent inhibition of depolariza-tion-evoked Ca2+ transients in oligodendroglial somata with a maximal effect (94 ± 3)% and an EC50 of 1.3 ±0.03 μM. This activity was mimicked by the CB2/CB2 agonist CP55,940, as well as by the endocannabinoids N-arachidonoyl-ethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), whereas the CB2 receptor se-lective agonist JWH133 was ineffective. The CB2 receptor antagonist AM251 (1 μM) also reduced the Ca2+ response evoked by high extracellular K+ and did not prevent the inhibition elicited by ACEA (3 μM). Nevertheless, the a-bility of ACEA and AEA to reduce depolarization-evoked Ca2+ transients was significantly reduced in oligodendro-cytes from CB2 receptor knockout mice, as well as by pretreatment with pertussis toxin. Bath application of the in-wardly rectifying K+ channels (Kir channels) blockers BaCl2 (300 μM) and CsCl2 (1 mM) reduced the size of volt-age-induced Ca2+ influx and partially prevented the inhibitory effect of ACEA. Our results indicate that eannabinoids inhibit depolarization-evoked Ca2+ transients in oligodendrocytes via CB2 receptor-independent and -dependent mech-anisms that involve the activation of PTX-sensitive Gi/o proteins and the blockade of Kir channels. C 2008 Wiley-Liss, Inc.关键词
大麻素类/CB2受体/少突胶质细胞/离子通道/钙/髓鞘化Key words
cannabinoids/CB2 receptors/oligodendrocyte/ion channel/calcium/myelinization分类
医药卫生引用本文复制引用
SUSANA MATO,ELENA ALBERDI,CATHERINE LEDENT,MASAHIKO WATANABE,AND CARLOS MATUTE..CB1 Cannabinoid Receptor-Dependent and -Independent Inhibition of Depolarization-Induced Calcium Influx in Oiigodendrocytes[J].神经损伤与功能重建,2009,4(1):48-59,12.基金项目
Supported by CIBERNED, Ministerio de Educacioon y Ciencia,Universidad del Pals Vasco,Gobierno Vasco,and the European Leukodystrophy Association.S.Mato was recipient of a J uan de la Cierva contract.The technical assistance of Hazel Goomez,Silvia Martinez and Onintza Lopez,as well as of the staff ftom the animal facility of the University of the Basque Country is kindly acknowledged. （）
