Nanodomain coupling between Ca2+ channels and Ca2+ sensors promotes fast and efficient transmitter release at a cortical GABAergic synapse
Nanodomain coupling between Ca2+ channels and Ca2+ sensors promotes fast and efficient transmitter release at a cortical GABAergic synapse
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DOI：
10.1016/j.neuron.2007.12.026
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发表时间：
2008-02-28
期刊：
影响因子：
16.2
通讯作者：
Jonas, Peter
中科院分区：
文献类型：
--
作者：
Bucurenciu, Iancu;Kulik, Akos;Jonas, Peter
一般认为，哺乳动物中枢突触的递质释放是由Ca 2+微区触发的，这意味着突触前Ca 2+通道和胞吐作用的Ca 2+传感器之间存在松散耦合。在这里，我们表明，钙离子通道亚基免疫反应是高度集中在GABA能突触前终端的活性区的假定小清蛋白在海马中的篮状细胞。配对记录结合突触前贴片移液管灌注显示，GABA释放在篮细胞-颗粒细胞突触是敏感的快钙螯合剂BAPTA的毫摩尔浓度，但不敏感的慢钙螯合剂EGTA。这些结果表明，Ca ~（2+）源和Ca ~（2+）传感器在该突触处紧密耦合，距离在10-20 nm范围内。Ca 2+内流-胞吐耦合模型进一步揭示耦合的紧密性增加了递质释放的功效、速度和时间精度。因此，紧密耦合有助于海马网络中的快速前馈和反馈抑制。
It is generally thought that transmitter release at mammalian central synapses is triggered by Ca2+ microdomains, implying loose coupling between presynaptic Ca2+ channels and Ca2+ sensors of exocytosis. Here we show that Ca2+ channel subunit immunoreactivity is highly concentrated in the active zone of GABAergic presynaptic terminals of putative parvalbumin-containing basket cells in the hippocampus. Paired recording combined with presynaptic patch pipette perfusion revealed that GABA release at basket cell-granule cell synapses is sensitive to millimolar concentrations of the fast Ca2+ chelator BAPTA but insensitive to the slow Ca2+ chelator EGTA. These results show that Ca2+ source and Ca2+ sensor are tightly coupled at this synapse, with distances in the range of 10-20 nm. Models of Ca2+ inflow-exocytosis coupling further reveal that the tightness of coupling increases efficacy, speed, and temporal precision of transmitter release. Thus, tight coupling contributes to fast feedforward and feedback inhibition in the hippocampal network.