Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca2+ channels via microdomain coupling.
Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca2+ channels via microdomain coupling.
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DOI：
10.1523/jneurosci.6104-11.2012
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发表时间：
2012-10-10
期刊：
影响因子：
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通讯作者：
Jonas P
中科院分区：
文献类型：
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作者：
Goswami SP;Bucurenciu I;Jonas P
突触前Ca ~（2+）通道与胞吐Ca ~（2+）感受器之间的耦合是突触传递的关键决定因素。从小清蛋白（PV）表达的中间神经元的诱发释放是由P/Q型Ca 2+通道的纳米结构域偶联触发的，而从胆囊收缩素（CCK）含有的中间神经元的释放是由N型通道的微结构域偶联产生的。纳米畴耦合具有若干功能优势，包括传输的速度和功效。一个潜在的缺点是突触前Ca 2+通道的随机开放可能会触发自发的递质释放。我们在大鼠海马颗粒细胞中解决了这种可能性，该细胞接收来自不同抑制源的会聚输入。细胞外Ca 2+浓度的降低和非选择性Ca 2+通道阻断剂Cd 2+均使颗粒细胞中微型IPSC（mIPSC）的频率降低约50%，表明突触前Ca 2+通道的开放有助于自发释放。应用选择性P/Q型Ca 2+通道阻断剂ω-agatoxin IVa没有可检测到的作用，而N型阻断剂ω-conotoxin GVIa和L型阻断剂尼莫地平都降低了mIPSC频率。此外，快速的Ca 2+螯合剂BAPTA-AM和缓慢的螯合剂EGTA-AM都降低了mIPSC频率，表明Ca 2+依赖性自发释放是由微区而不是纳米区偶联触发的。CB 1受体激动剂WIN 55212-2也降低自发释放;这种作用被预先应用ω-芋螺毒素GVIa阻断，表明在CCK表达的中间神经元的末端产生了主要部分的Ca 2+依赖性自发释放。突触前N-和L-型Ca ~（2+）通道自发开放所产生的紧张性抑制可能对海马的信息加工有重要作用。
The coupling between presynaptic Ca2+ channels and Ca2+ sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca2+ channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca2+ channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca2+ concentration and the unselective Ca2+ channel blocker Cd2+ reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca2+ channels contributes to spontaneous release. Application of the selective P/Q-type Ca2+ channelblocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca2+ chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca2+-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB1 receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca2+-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca2+ channels may be important for hippocampal information processing.