LOCALIZATION OF MULTIPLE NEUROTRANSMITTERS IN SURGICALLY DERIVED SPECIMENS OF HUMAN ATRIAL GANGLIA
LOCALIZATION OF MULTIPLE NEUROTRANSMITTERS IN SURGICALLY DERIVED SPECIMENS OF HUMAN ATRIAL GANGLIA
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DOI：
10.1016/j.neuroscience.2009.09.001
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发表时间：
2009-12-15
期刊：
影响因子：
3.3
通讯作者：
Armour, J. A.
中科院分区：
文献类型：
--
作者：
Hoover, D. B.;Isaacs, E. R.;Armour, J. A.
心脏固有神经系统功能障碍与房性和室性心律失常的发生有关。虽然这一系统已经在动物模型中进行了广泛的研究，但对人类内在的心脏神经系统的了解要少得多。这项研究是为了从解剖学上确定与人类心脏的右房神经节丛(RAGP)相关的神经递质。在心胸外科手术期间，从8名患者的心外膜脂肪组织中收集含有部分RAGP的活检组织，并进行免疫荧光检测特定的神经元标记。通过共聚焦显微镜评价标记的共定位。大多数心脏固有神经元胞体对胆碱能标志胆碱乙酰转移酶和氮能标志神经元型一氧化氮合酶呈免疫反应。心脏固有神经元的一个亚群也对去甲肾上腺素能标记进行了染色。虽然大多数心脏固有神经元接受胆碱能神经支配，如高亲和力胆碱转运体的点状免疫染色，但一些神经元缺乏胆碱能输入。此外，肽能、氮能和去甲肾上腺素能神经为心内神经节提供了大量的神经支配。这些发现表明，人RAGP具有复杂的神经化学解剖结构，包括其大部分神经元存在胆碱能/氮能双重表型，部分神经元存在去甲肾上腺素能标志，以及许多神经化学上不同的神经支配。多种神经递质在控制心脏内源性神经元和介导心脏传出信号中的作用表明，有可能成为预防心律失常的新的治疗靶点。(C)2009年IBRO。爱思唯尔有限公司出版。保留所有权利。
Dysfunction of the intrinsic cardiac nervous system is implicated in the genesis of atrial and ventricular arrhythmias. While this system has been studied extensively in animal models, far less is known about the intrinsic cardiac nervous system of humans. This study was initiated to anatomically identify neurotransmitters associated with the right atrial ganglionated plexus (RAGP) of the human heart. Biopsies of epicardial fat containing a portion of the RAGP were collected from eight patients during cardiothoracic surgery and processed for immunofluorescent detection of specific neuronal markers. Colocalization of markers was evaluated by confocal microscopy. Most intrinsic cardiac neuronal somata displayed immunoreactivity for the cholinergic marker choline acetyltransferase and the nitrergic marker neuronal nitric oxide synthase. A subpopulation of intrinsic cardiac neurons also stained for noradrenergic markers. While most intrinsic cardiac neurons received cholinergic innervation evident as punctate immunostaining for the high affinity choline transporter, some lacked cholinergic inputs. Moreover, peptidergic, nitrergic, and noradrenergic nerves provided substantial innervation of intrinsic cardiac ganglia. These findings demonstrate that the human RAGP has a complex neurochemical anatomy, which includes the presence of a dual cholinergic/nitrergic phenotype for most of its neurons, the presence of noradrenergic markers in a subpopulation of neurons, and innervation by a host of neurochemically distinct nerves. The putative role of multiple neurotransmitters in controlling intrinsic cardiac neurons and mediating efferent signaling to the heart indicates the possibility of novel therapeutic targets for arrhythmia prevention. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.