Mouse models of sepsis elicit spontaneous action potential discharge and enhance intracellular Ca2+ signaling in postganglionic sympathetic neurons
Mouse models of sepsis elicit spontaneous action potential discharge and enhance intracellular Ca2+ signaling in postganglionic sympathetic neurons
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脓毒症小鼠模型引起自发动作电位放电并增强节后交感神经元的细胞内 Ca2 信号传导
DOI：
10.1016/j.neuroscience.2014.10.039
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发表时间：
2015
期刊：
影响因子：
3.3
通讯作者：
A. Lomax
中科院分区：
文献类型：
--
作者：
M. Lukewich;A. Lomax
脓毒症是一种严重的全身性炎症性疾病，其迅速激活交感神经系统以增强节后交感神经元和肾上腺嗜铬细胞的儿茶酚胺分泌。虽然增加节前驱动到节后交感神经组织已经知道有助于这种反应相当长的一段时间，只是最近才确定，脓毒症也有肾上腺嗜铬细胞Ca2+信号和肾上腺素释放的直接影响。在本研究中，我们描述了脓毒症对节后交感神经元功能的直接影响。使用小鼠败血症的内毒素血症模型，我们发现几乎四分之一的节后神经元获得了激发自发动作电位的能力，而对照小鼠的细胞中没有这种能力。自发放电的神经元具有显着较低的基强度和发射了大量的动作电位的两倍的基强度相比，从对照组小鼠的神经元。脓毒症并没有显着影响电压门控钙电流。然而，全球Ca2+信号增强，从1至24小时内毒素血症小鼠分离的节后神经元。在盲肠结扎和穿孔脓毒症模型期间观察到高K+刺激的Ca2+瞬变幅度的类似增加。脓毒症期间产生的增强的兴奋性和Ca2+信号传导可能放大了增加的节前驱动对节后神经元释放去甲肾上腺素的影响。这一点很重要，因为交感神经元是脓毒症期间激活的抗炎自主反射的组成部分。
Sepsis is a severe systemic inflammatory disorder that rapidly activates the sympathetic nervous system to enhance catecholamine secretion from postganglionic sympathetic neurons and adrenal chromaffin cells. Although an increase in preganglionic drive to postganglionic sympathetic tissues has been known to contribute to this response for quite some time, only recently was it determined that sepsis also has direct effects on adrenal chromaffin cell Ca2+signaling and epinephrine release. In the present study, we characterized the direct effects of sepsis on postganglionic sympathetic neuron function. Using the endotoxemia model of sepsis in mice, we found that almost a quarter of postganglionic neurons acquired the ability to fire spontaneous action potentials, which was absent in cells from control mice. Spontaneously firing neurons possessed significantly lower rheobases and fired a greater number of action potentials at twice the rheobase compared to neurons from control mice. Sepsis did not significantly affect voltage-gated Ca2+currents. However, global Ca2+signaling was enhanced in postganglionic neurons isolated from 1 to 24 h endotoxemic mice. A similar increase in the amplitude of high-K+-stimulated Ca2+transients was observed during the cecal ligation and puncture model of sepsis. The enhanced excitability and Ca2+signaling produced during sepsis likely amplify the effect of increased preganglionic drive on norepinephrine release from postganglionic neurons. This is important, as sympathetic neurons are integral to the anti-inflammatory autonomic reflex that is activated during sepsis.
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影响因子：
4.4
作者：
V. Sanders;R. A. Baker;D. Ramer-Quinn;Deborah J. Kasprowicz;B. Fuchs;N. Street
通讯作者：
V. Sanders;R. A. Baker;D. Ramer-Quinn;Deborah J. Kasprowicz;B. Fuchs;N. Street
影响因子：
158.5
作者：
Martin, GS;Mannino, DM;Moss, M
通讯作者：
Moss, M
全身内毒素在大鼠脊髓交感神经区诱导 Fos 样免疫反应性。
DOI：
10.1016/0165-1838(95)80001-q
发表时间：
1995
期刊：
Journal of the autonomic nervous system
影响因子：
--
作者：
Tkacs,NC;Strack,AM
通讯作者：
Strack,AM
内毒素后窦主动脉去神经大鼠的交感肾上腺激活。
DOI：
10.1152/ajpregu.1991.260.4.r739
发表时间：
1991
期刊：
The American journal of physiology
影响因子：
--
作者：
Zhou,ZZ;Wurster,RD;Qi,M;Jones,SB
通讯作者：
Jones,SB