Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels.
Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels.
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DOI：
10.1038/nn.3563
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发表时间：
2013-12
影响因子：
25
通讯作者：
Volynski, Kirill E.
中科院分区：
文献类型：
--
作者：
Ermolyuk, Yaroslav S.;Alder, Felicity G.;Surges, Rainer;Pavlov, Ivan Y.;Timofeeva, Yulia;Kullmann, Dimitri M.;Volynski, Kirill E.
电压门控钙通道（VGCC）在自发性微小神经递质释放中的作用尚未完全了解。在这里，我们表明，随机开放的P/Q-，N-和R-型VGCC占所有自发性谷氨酸释放在大鼠培养的海马突触的50%，和R-型通道发挥更大的作用，在自发的比动作电位诱发的胞吐。VGCC依赖的“迷你”表现出类似的敏感性突触前钙螯合诱发释放，主张直接触发自发释放的瞬时空间局部化的Ca 2+结构域。实验约束的三维扩散模型的Ca 2+流入-胞吐耦合是一致的VGCC的小海马突触的活动区中的集群分布，并表明，自发VGCC开口可以解释实验观察到的VGCC依赖的minis，虽然单通道开放触发释放的概率低。因此，不相关的随机VGCC开放是自发谷氨酸释放的主要触发因素，不同的通道亚型具有不同的作用。
The role of voltage-gated Ca2+ channels (VGCCs) in spontaneous miniature neurotransmitter release is incompletely understood. Here we show that stochastic opening of P/Q-, N-, and R-type VGCCs accounts for ~50% of all spontaneous glutamate release at rat cultured hippocampal synapses, and that R-type channels play a far greater role in spontaneous than in action potential-evoked exocytosis. VGCC-dependent ‘minis’ show similar sensitivity to presynaptic Ca2+ chelation as evoked release, arguing for direct triggering of spontaneous release by transient spatially localized Ca2+ domains. Experimentally constrained three-dimensional diffusion modeling of Ca2+ influx-exocytosis coupling is consistent with clustered distribution of VGCCs in the active zone of small hippocampal synapses, and shows that spontaneous VGCCs openings can account for the experimentally observed VGCC-dependent minis, although single channel openings trigger release with low probability. Uncorrelated stochastic VGCC opening is thus a major trigger for spontaneous glutamate release, with differential roles for distinct channel subtypes.
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影响因子：
25
作者：
Bucurenciu, Iancu;Bischofberger, Josef;Jonas, Peter
通讯作者：
Jonas, Peter
影响因子：
16.2
作者：
Novak P;Gorelik J;Vivekananda U;Shevchuk AI;Ermolyuk YS;Bailey RJ;Bushby AJ;Moss GW;Rusakov DA;Klenerman D;Kullmann DM;Volynski KE;Korchev YE
通讯作者：
Korchev YE
影响因子：
64.5
作者：
GEPPERT, M;GODA, Y;SUDHOF, TC
通讯作者：
SUDHOF, TC
影响因子：
5.3
作者：
Meinrenken, CJ;Borst, JGG;Sakmann, B
通讯作者：
Sakmann, B
DOI：
10.1523/jneurosci.6104-11.2012
发表时间：
2012-10-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Goswami SP;Bucurenciu I;Jonas P
通讯作者：
Jonas P