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心肌细胞通过泛连接蛋白-1通道触发的缺血诱导ATP释放激活交感神经纤维。

Ischemia triggered ATP release through Pannexin-1 channel by myocardial cells activates sympathetic fibers.

作者信息

Dong Feng, Yang Xiang-Jun, Jiang Ting-Bo, Chen Ying

机构信息

Department of Cardiology, The First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu, China.

Department of Cardiology, The First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu, China.

出版信息

Microvasc Res. 2016 Mar;104:32-7. doi: 10.1016/j.mvr.2015.11.005. Epub 2015 Nov 18.

DOI:10.1016/j.mvr.2015.11.005
PMID:26596404
Abstract

The cardiovascular system is extensively innervated by the autonomic nervous system, and the autonomic modulation including sympathetic innervation is crucial to the function of heart during normal and ischemic conditions. Severe myocardial ischemia could cause acute myocardial infarction, which is one of the leading diseases in the world. Thus studying the sympathetic modulation during ischemia could reduce the probability of myocardial infarction and further heart failure. The neurotransmitter ATP is released by myocardial cells during ischemia; however, the effect of ATP release remains elusive. We examined whether ATP released during ischemia functions as a neurotransmitter that activates sympathetic nerve in the heart. A novel technique of recording the sympathetic fiber calcium imaging in mouse cardiac tissue slices was used. We have applied the Cre/loxP system to specifically express GCaMP3, a genetically encoded calcium indicator, in the sympathetic nerve. Using this technique, we found that ATP released by myocardial cells through Pannexin-1 channel during ischemia could evoke calcium responses in cardiac sympathetic nerve fibers. Our study provides a new approach to study the cell and nerve interaction in the cardiac system, as well as a new understanding of ATP function during ischemia.

摘要

心血管系统由自主神经系统广泛支配,包括交感神经支配在内的自主调节对于心脏在正常和缺血状态下的功能至关重要。严重的心肌缺血可导致急性心肌梗死,这是世界上主要的疾病之一。因此,研究缺血期间的交感神经调节可以降低心肌梗死和进一步心力衰竭的可能性。神经递质ATP在缺血期间由心肌细胞释放;然而,ATP释放的作用仍不清楚。我们研究了缺血期间释放的ATP是否作为一种神经递质激活心脏中的交感神经。我们使用了一种在小鼠心脏组织切片中记录交感神经纤维钙成像的新技术。我们应用Cre/loxP系统在交感神经中特异性表达基因编码的钙指示剂GCaMP3。使用该技术,我们发现缺血期间心肌细胞通过泛连接蛋白-1通道释放的ATP可引起心脏交感神经纤维中的钙反应。我们的研究为研究心脏系统中的细胞与神经相互作用提供了一种新方法,以及对缺血期间ATP功能的新认识。

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