Extracellular Protons Mediate Presynaptic Homeostatic Potentiation at the Mouse Neuromuscular Junction.
Extracellular Protons Mediate Presynaptic Homeostatic Potentiation at the Mouse Neuromuscular Junction.
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细胞外质子介导小鼠神经肌肉连接处突触前稳态增强。
DOI：
10.1016/j.neuroscience.2021.01.036
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发表时间：
2021-07-15
期刊：
影响因子：
3.3
通讯作者：
Lindgren, Clark A.
中科院分区：
文献类型：
--
作者：
Zhu, Yiyang;Warrenfelt, Claire I. C.;Flannery, Jill C.;Lindgren, Clark A.
在脊椎动物神经肌肉接头（NMJ），突触前稳态增强（PHP）是指当突触后烟碱乙酰胆碱受体（nAChR）被部分阻断时，通过增加量子含量（QC）来上调神经递质释放。PHP的机制尚未完全阐明。特别是，推定的逆行信号的身份仍然是一个谜。我们研究了酸敏感离子通道（ASICs）和细胞外质子在小鼠NMJ介导PHP中的作用。我们发现，使用benzamil，psalmotoxin-1（PcTx 1）或mambalgin-3（Mamb 3）阻断AISC可以预防PHP。同样，从pH 7.4到7.2的细胞外酸化引发了QC的显著的、可逆的增加，并且这种增加可以被PcTx 1阻止。有趣的是，酸性盐水（pH 7.2）也排除了PHP的后续诱导。使用免疫荧光，我们观察到在NMJ的ASIC 2a和ASIC 1亚基。我们的结果表明质子和ASIC通道参与激活小鼠NMJ的PHP。我们推测部分阻断nAChR导致突触间隙的pH适度降低（约0.2 pH单位），这激活了突触前神经末梢上的ASIC通道。
At the vertebrate neuromuscular junction (NMJ), presynaptic homeostatic potentiation (PHP) refers to the upregulation of neurotransmitter release via an increase in quantal content (QC) when the postsynaptic nicotinic acetylcholine receptors (nAChRs) are partially blocked. The mechanism of PHP has not been completely worked out. In particular, the identity of the presumed retrograde signal is still a mystery. We investigated the role of acid-sensing ion channels (ASICs) and extracellular protons in mediating PHP at the mouse NMJ. We found that blocking AISCs using benzamil, psalmotoxin-1 (PcTx1), or mambalgin-3 (Mamb3) prevented PHP. Likewise, extracellular acidification from pH 7.4 to 7.2 triggered a significant, reversable increase in QC and this increase could be prevented by PcTx1. Interestingly, an acidic saline (pH 7.2) also precluded the subsequent induction of PHP. Using immunofluorescence we observed ASIC2a and ASIC1 subunits at the NMJ. Our results indicate that protons and ASIC channels are involved in activating PHP at the mouse NMJ. We speculate that the partial blockade of nAChRs leads to a modest decrease in the pH of the synaptic cleft (~ 0.2 pH units) and this activates ASIC channels on the presynaptic nerve terminal.
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影响因子：
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