Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals.
Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals.
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DOI：
10.1038/ncomms7557
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发表时间：
2015-04-20
影响因子：
16.6
通讯作者：
Nusser, Zoltan
中科院分区：
文献类型：
--
作者：
Lenkey, Nora;Kirizs, Tekla;Holderith, Noemi;Mate, Zoltan;Szabo, Gabor;Vizi, E. Sylvester;Hajos, Norbert;Nusser, Zoltan
含胆囊收缩素的中间神经元释放GABA受1型大麻素受体（CB1）调节。在这里，我们验证了CB1介导的GABA释放调节的强度与轴突末端CB1含量有关的假设。篮状细胞钮扣的CB1含量比树突层神经支配细胞（DLI）平均高78%，这是由于钮扣表面更大，CB1密度更高。CB1拮抗剂AM251在篮状细胞钮扣中引起54%的动作电位诱发[Ca2+]增加，但在DLI细胞中没有。然而，AM251的作用与单个钮扣的CB1免疫反应性无关。此外，CB1激动剂以细胞类型和CB1含量无关的方式降低[Ca2+]。复制免疫金标记显示CB1与Cav2.2 Ca2+通道亚基共定位。我们的数据表明，只有CB1s的一个亚群，在其靶Cav2.2通道的纳米距离内，负责内源性大麻素介导的GABA释放调节。一个简单的受体数函数关系模型表明受体含量和配体效应之间呈正相关。在这里，作者证明了1型大麻素受体（CB1）调节GABA释放的程度不能从轴突末端的CB1含量来预测。
The release of GABA from cholecystokinin-containing interneurons is modulated by type-1 cannabinoid receptors (CB1). Here we tested the hypothesis that the strength of CB1-mediated modulation of GABA release is related to the CB1 content of axon terminals. Basket cell boutons have on average 78% higher CB1 content than those of dendritic-layer-innervating (DLI) cells, a consequence of larger bouton surface and higher CB1 density. The CB1 antagonist AM251 caused a 54% increase in action potential-evoked [Ca2+] in boutons of basket cells, but not in DLI cells. However, the effect of AM251 did not correlate with CB1 immunoreactivity of individual boutons. Moreover, a CB1 agonist decreased [Ca2+] in a cell type- and CB1-content-independent manner. Replica immunogold labelling demonstrated the colocalization of CB1 with the Cav2.2 Ca2+ channel subunit. Our data suggest that only a subpopulation of CB1s, within nanometre distances from their target Cav2.2 channels, are responsible for endocannabinoid-mediated modulation of GABA release. A simple model for receptor number–function relationships dictates a positive correlation between receptor content and ligand effect. Here, the authors demonstrate that the degree of type-1 cannabinoid receptor (CB1)-modulated GABA release cannot be predicted from CB1 content of axon terminals.
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DOI：
10.1523/jneurosci.6238-09.2010
发表时间：
2010-06-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lee SH;Földy C;Soltesz I
通讯作者：
Soltesz I
影响因子：
2.9
作者：
de Vivo L;Melone M;Rothstein JD;Conti F
通讯作者：
Conti F
影响因子：
3.4
作者：
Gulyas, AI;Cravatt, BF;Freund, TF
通讯作者：
Freund, TF
影响因子：
5.3
作者：
Katona, István;Urbán, Gabriella M.;Freund, Tamás F.
通讯作者：
Freund, Tamás F.
影响因子：
25
作者：
Dudok, Barna;Barna, Laszlo;Ledri, Marco;Szabo, Szilard I.;Szabadits, Eszter;Pinter, Balazs;Woodhams, Stephen G.;Henstridge, Christopher M.;Balla, Gyula Y.;Nyilas, Rita;Varga, Csaba;Lee, Sang-Hun;Matolcsi, Mate;Cervenak, Judit;Kacskovics, Imre;Watanabe, Masahiko;Sagheddu, Claudia;Melis, Miriam;Pistis, Marco;Soltesz, Ivan;Katona, Istvan
通讯作者：
Katona, Istvan