Altered atrial neurotransmitter release in transgenic p75(-/-) and gp130 KO mice.
Altered atrial neurotransmitter release in transgenic p75(-/-) and gp130 KO mice.
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DOI：
10.1016/j.neulet.2012.08.089
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发表时间：
2012-10-31
影响因子：
2.5
通讯作者：
Habecker BA
中科院分区：
文献类型：
--
作者：
Hasan W;Woodward WR;Habecker BA
心率由支配窦房结和心脏传导系统的刺激性交感神经和抑制性副交感神经控制。去甲肾上腺素（NE）的交感神经释放和乙酰胆碱（ACh）的副交感神经释放由中枢神经系统控制，并且由心房内的递质释放的突触前抑制控制。心脏交感神经传递相对于副交感神经传递的增加是病理性的，因为它可导致心律紊乱、儿茶酚胺能毒性和心律失常或纤颤的发展。缺乏p75神经营养因子受体（p75−/−）的小鼠心房NE升高，但心率较低，提示自主神经失调。类似地，交感神经元缺乏gp 130细胞因子受体（gp 130 KO）的小鼠在迷走神经刺激后具有正常心率但增强的心动过缓。目前尚不清楚的是，这些动物的心脏自主神经紊乱是否反映了神经活动的全身性改变，或者是否涉及神经递质储存或释放的局部缺陷。为了研究局部刺激诱发的神经递质释放，我们开发了一种新的方法，用于在离体心房场刺激后同时定量NE和ACh。使用HPLC电化学检测NE，HPLC质谱法检测ACh，我们发现场刺激后p75−/−心房的NE释放受损，而gp 130 KO心房的ACh含量和释放升高。因此，心房外植体局部递质释放的改变与心率控制的体内缺陷一致，表明这些小鼠自主神经传递的外周改变。
Heart rate is controlled by stimulatory sympathetic and inhibitory parasympathetic nerves innervating the sino-atrial node and cardiac conduction system. Sympathetic release of norepinephrine (NE) and parasympathetic release of acetylcholine (ACh) are controlled by the central nervous system, and by pre-synaptic inhibition of transmitter release within the atria. An increase in cardiac sympathetic transmission relative to parasympathetic transmission is pathological as it can lead to disturbances in heart rhythm, catecholaminergic toxicity and development of arrhythmias or fibrillation. Mice lacking the p75 neurotrophin receptor (p75−/−) have elevated atrial NE but a low heart rate suggesting autonomic dysregulation. Similarly, mice whose sympathetic neurons lack the gp130 cytokine receptor (gp130 KO) have a normal heart rate but enhanced bradycardia after vagal nerve stimulation. What is unclear is whether cardiac autonomic disturbances in these animals reflect systemic alterations in nerve activity or whether localized defects in neurotransmitter stores or release are involved. To examine local stimulus-evoked release of neurotransmitters, we have developed a novel method for simultaneous quantification of both NE and ACh after ex-vivo atrial field stimulation. Using HPLC with electrochemical detection for NE, and HPLC with mass spectrometry for ACh, we found that following field stimulation NE release was impaired in p75−/− atria while ACh content and release was elevated in gp130 KO atria. Thus, alterations in localized transmitter release from atrial explants are consistent with in vivo deficits in heart rate control, suggesting peripheral alterations in autonomic transmission in these mice.
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DOI：
10.1523/jneurosci.3503-08.2009
发表时间：
2009-04-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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10.1152/ajpheart.00409.2009
发表时间：
2009-09-01
影响因子：
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作者：
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通讯作者：
Habecker, Beth A.
影响因子：
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作者：
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