Presynaptic mechanism underlying cAMP-dependent synaptic potentiation
Presynaptic mechanism underlying cAMP-dependent synaptic potentiation
复制标题
DOI：
10.1523/jneurosci.0999-04.2004
复制
发表时间：
2004-06-02
影响因子：
5.3
通讯作者：
Takahashi, T
中科院分区：
文献类型：
--
作者：
Kaneko, M;Takahashi, T
腺苷环化酶激活剂Forskolin在突触前促进了许多突触的突触传递，但这种作用的确切细胞内机制尚不清楚。我们在Hold的花冠上研究了这个问题，在那里可以同时进行突触前和突触后的全细胞记录。在突触前终末沐浴Forsklin或细胞内应用cAMP可强烈增强EPSCs。Forsklin诱导的突触增强与释放概率(P)和可释放突触小泡(N)的增加有关。Forsklin对突触前Ca~(2+)电流或K~+电流的峰值无影响，提示cAMP的主要靶点位于钙内流的下游。细胞内应用选择性EPAC激动剂8-(4-氯苯硫基)-2‘-O-甲基-cAMP可增强突触前终末EPSCs，提示EPAC是cAMP诱导突触增强的主要靶点。我们的结论是，神经末梢cAMP浓度的增加通过激活Hold花瓣处的EPAC通路，增加了释放几率和可释放小泡的数量，从而促进了递质的释放。
The adenylyl cyclase activator forskolin presynaptically facilitates synaptic transmission at many synapses, but the exact intracellular mechanism underlying this effect is not known. We studied this issue at the calyx of Held, where it is possible to make simultaneous presynaptic and postsynaptic whole-cell recordings. Bath application of forskolin or intracellular application of cAMP into presynaptic terminals strongly potentiated EPSCs. The forskolin-induced synaptic potentiation was associated with increases in release probability (P) and number of releasable synaptic vesicles (N). Forskolin had no effect on the peak amplitudes of presynaptic Ca2+ currents or K+ currents, suggesting that the main target of cAMP resides in downstream of Ca2+ influx. Intracellular application of the selective Epac agonist 8-(4-chlorophenylthio)-2'-O-methyl-cAMP into presynaptic terminals potentiated EPSCs, suggesting that Epac is the main target of cAMP-induced synaptic potentiation. We conclude that an increase in cAMP concentration in the nerve terminal facilitates transmitter release by increasing both release probability and number of releasable vesicles via activating the Epac pathway at the calyx of Held.