论文部分内容阅读
Ca2+稳态平衡的调节在少突胶质细胞功能和存活中起重要作用。大麻素CB1和CB2受体在许多细胞中调节Ca2+水平和/或K+电流。本文利用培养的少突胶质细胞中,通过增高细胞外K+浓度(50 mM诱导膜去极化,研究大麻素复合物在此过程引发钙内流中的作用。CB2受体激动剂ACEA导致去极化诱导的少突胶质细胞胞浆的Ca2+瞬变表达浓度依赖性抑制,最大效应为(94±3)%,半效应浓度(EC50)为(1.3±0.03)μM。这种作用可被CB2/CB2激动剂CP55、940、内源性大麻素类AEA和2-AG所模拟,但是CB2受体选择性激动剂J WH133没有作用。CB2受体拮抗剂AM251(1μM)也可减少细胞外高K+诱导的Ca2+反应,但不能防止ACEA(3μM)诱发的抑制效应。然而,ACEA和AEA减少去极化诱导的Ca2+瞬变的能力在CB2受体敲除小鼠和经百日咳毒素预处理的少突胶质细胞中明显降低。内流性K+通道阻断剂BaCl2(300μM)和CsCl2(1 mM)降低电压诱导的Ca2+内流并部分阻断ACEA的抑制效应。本文表明,大麻素抑制少突胶质细胞中去极化诱导的Ca2+瞬变是通过包括PTX-敏感的Gi/o蛋白和阻断K+内流通道的CB2受体依赖性和非依赖性机制。
The regulation of homeostatic balance of Ca2 plays an important role in oligodendrocyte function and survival. The cannabinoid CB1 and CB2 receptors regulate Ca2 + levels and / or K + currents in many cells. In this paper, the effect of cannabinoid complexes on calcium influx in this process was investigated by increasing extracellular K + concentrations (50 mM induced membrane depolarization) in cultured oligodendrocytes.CB2 agonist ACEA led to Polarization-induced oligodendrocyte cytoplasmic Ca 2+ transients were inhibited in a concentration-dependent manner with a maximal effect of (94 ± 3)% and an EC50 of (1.3 ± 0.03) μM. This effect was CB2 / CB2 agonist CP55, 940, endocannabinoids AEA and 2-AG, but CB2 receptor selective agonist J WH133 had no effect.CB2 receptor antagonist AM251 (1 μM) also decreased extracellular High K + -induced Ca2 + response but failed to prevent ACEA (3μM) -induced inhibitory effect However, the ability of ACEA and AEA to reduce depolarization-induced Ca2 + transients in CB2 receptor knockout mice and Pertussis toxin-pretreated Oligodendrocytes were significantly decreased.The influx of K + channel blockers BaCl2 (300μM) and CsCl2 (1mM) reduced the voltage-induced Ca2 + influx and partially blocked the inhibitory effect of ACEA.This paper shows that the inhibition of cannabinoids is less Depolarization-induced Ca2 + transients in the oligodendrocytes were induced by the inclusion of PTX-sensitive Gi / o proteins and K + off the CB2 receptor-dependent and independent mechanisms flow channel.