Autocrine activation of nicotinic acetylcholine receptors contributes to Ca2+ spikes in mouse myotubes during myogenesis
Autocrine activation of nicotinic acetylcholine receptors contributes to Ca2+ spikes in mouse myotubes during myogenesis
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DOI：
10.1113/jphysiol.2005.091439
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发表时间：
2005-10-01
影响因子：
5.5
通讯作者：
Lorenzon, P
中科院分区：
文献类型：
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作者：
Bandi, E;Bernareggi, A;Lorenzon, P
人们普遍认为烟碱乙酰胆碱受体（nAChR）通道活性在肌生成过程中控制成肌细胞融合成肌管。在这项研究中，我们探讨了小鼠细胞模型中细胞融合后 nAChR 通道的可能作用。使用视频成像技术，我们发现胚胎肌肉 nAChR 通道开放有助于细胞内 Ca2+ 浓度 ([Ca2+](i)) 的自发瞬变，并导致神经支配前发育中肌管的抽搐特征。此外，我们在肌管中观察到胆碱乙酰转移酶免疫反应性，并且在细胞外溶液中检测到乙酰胆碱样化合物。因此，我们认为 nAChR 通道的自分泌激活会引起 [Ca2+](i) 峰值和收缩。 nAChR 通道的自发开放可能是一种替代机制，尽管效率较低。我们还报告称，阻断 nAChR 会导致细胞存活率显着降低，这可以通过培养物中肌管数量的减少来检测。这使我们推测 nAChR 的自分泌激活可能具有功能作用。通过触发机械活动，这种激活可以代表一种确保在没有神经的情况下肌管的营养性的策略。
It is widely accepted that nicotinic acetylcholine receptor (nAChR) channel activity controls myoblast fusion into myotubes during myogenesis. In this study we explored the possible role of nAChR channels after cell fusion in a murine cell model. Using videoimaging techniques we showed that embryonic muscle nAChR channel openings contribute to the spontaneous transients of intracellular concentration of Ca2+ ([Ca2+](i)) and to twitches characteristic of developing myotubes before innervation. Moreover, we observed a choline acetyltransferase immunoreactivity in the myotubes and we detected an acetylcholine-like compound in the extracellular solution. Therefore, we suggest that the autocrine activation of nAChR channels gives rise to [Ca2+](i) spikes and contractions. Spontaneous openings of the nAChR channels may be an alternative, although less efficient, mechanism. We report also that blocking the nAChRs causes a significant reduction in cell survival, detectable as a decreased number of myotubes in culture. This led us to hypothesize a possible functional role for the autocrine activation of the nAChRs. By triggering mechanical activity, such activation could represent a strategy to ensure the trophism of myotubes in the absence of nerves.