Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents.
Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents.
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DOI：
10.1371/journal.pone.0174915
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Andresen MC
中科院分区：
文献类型：
--
作者：
Hofmann ME;Andresen MC
胞吐过程中融合的囊泡膜的再循环对维持神经传递是必不可少的。GT3发动蛋白参与夹断膜以完成内吞作用，并且可以被dynasore抑制，导致有释放能力的突触囊泡的活性依赖性耗尽。在大鼠脑干切片中，我们研究了dynasore对三种不同模式的谷氨酸释放的影响-自发的，诱发的，和异步释放-在孤束（ST）输入孤束核（NTS）中的神经元。间歇性突发刺激ST穿插暂停刺激允许检查这三种模式在每个神经元连续。应用100 μM dynasore可迅速增加自发EPSC（sEPSC）频率，随后抑制ST诱发EPSC（ST-EPSC）和异步EPSC。ST-EPSC失败的发生并不伴随着振幅降低，这种模式与传导阻滞比囊泡释放概率降低更一致。这两个结果都不表明dynasore中断了内吞作用。dynasore响应曲线类似于强烈的突触前TRPV 1激活。TRPV 1拮抗剂辣椒平未能防止dynasore增加sEPSC频率，但防止了ST-EPSC的阻滞。相比之下，TRPV 1拮抗剂JNJ 17203212阻止了具有TRPV 1表达ST输入的神经元中dynasore的两种作用。然而，在缺乏TRPV 1表达ST输入的神经元中，dynasore迅速增加sEPSC速率，随后阻断ST诱发的EPSC。总之，我们的研究结果表明，ST-NTS传输dynasore行动是TRPV 1独立的和变化的mammatergic传输是不一致的囊泡回收和内吞作用的变化。
The recycling of vesicle membrane fused during exocytosis is essential to maintaining neurotransmission. The GTPase dynamin is involved in pinching off membrane to complete endocytosis and can be inhibited by dynasore resulting in activity-dependent depletion of release-competent synaptic vesicles. In rat brainstem slices, we examined the effects of dynasore on three different modes of glutamate release–spontaneous, evoked, and asynchronous release–at solitary tract (ST) inputs to neurons in the nucleus of the solitary tract (NTS). Intermittent bursts of stimuli to the ST interspersed with pauses in stimulation allowed examination of these three modes in each neuron continuously. Application of 100 μM dynasore rapidly increased the spontaneous EPSC (sEPSC) frequency which was followed by inhibition of both ST-evoked EPSCs (ST-EPSC) as well as asynchronous EPSCs. The onset of ST-EPSC failures was not accompanied by amplitude reduction–a pattern more consistent with conduction block than reduced probability of vesicle release. Neither result suggested that dynasore interrupted endocytosis. The dynasore response profile resembled intense presynaptic TRPV1 activation. The TRPV1 antagonist capsazepine failed to prevent dynasore increases in sEPSC frequency but did prevent the block of the ST-EPSC. In contrast, the TRPV1 antagonist JNJ 17203212 prevented both actions of dynasore in neurons with TRPV1-expressing ST inputs. In a neuron lacking TRPV1-expressing ST inputs, however, dynasore promptly increased sEPSC rate followed by block of ST-evoked EPSCs. Together our results suggest that dynasore actions on ST-NTS transmission are TRPV1-independent and changes in glutamatergic transmission are not consistent with changes in vesicle recycling and endocytosis.