Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH, Amsterdam, The Netherlands.
Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3534-9. doi: 10.1073/pnas.1118167109. Epub 2012 Feb 13.
The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that CB(2)Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP(3)R-dependent opening of Ca(2+)-activated Cl(-) channels. To investigate the functional role of CB(2)R activation, we induced neuronal firing and observed a CB(2)R-mediated reduction in firing frequency. The description of this unique CB(2)R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.
内源性大麻素（eCB）系统广泛表达于中枢神经系统（CNS），神经元中的 1 型大麻素受体的功能已有大量文献记载。相比之下，CNS 中的 2 型大麻素受体（CB2Rs）知之甚少。在这里，我们发现 CB2Rs 位于啮齿动物内侧前额叶皮质（mPFC）II/III 层的锥体神经元细胞内，其激活导致 IP3R 依赖性 Ca2+激活 Cl-通道开放。为了研究 CB2R 激活的功能作用，我们诱导神经元放电，并观察到 CB2R 介导的放电频率降低。这种独特的 CB2R 介导的信号通路描述，控制着神经元的兴奋性，拓宽了我们对内源性大麻素系统对大脑功能影响的认识。
