Neuroendocrine properties of intrinsic cardiac adrenergic cells in fetal rat heart
Neuroendocrine properties of intrinsic cardiac adrenergic cells in fetal rat heart
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DOI：
10.1152/ajpheart.00591.2004
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发表时间：
2005-02-01
影响因子：
4.8
通讯作者：
Ewy, GA
中科院分区：
文献类型：
--
作者：
Huang, MH;Bahl, JJ;Ewy, GA
发育中的大鼠心脏内源性心脏肾上腺素能（伊卡）细胞构成了一个新的参与心脏调节的肾上腺素能信号系统。伊卡细胞的调节机制仍有待确定。免疫组化显示伊卡细胞具有儿茶酚胺生物合成酶酪氨酸羟化酶（TH）和苯乙醇胺N-甲基转移酶（PNMT）。在交感神经支配前胎鼠心脏中也检测到TH和PNMP的mRNA。去甲肾上腺素转运体（NET）的免疫反应性定位于大鼠心脏组织和原代细胞培养的伊卡细胞。对于功能研究，通过比率荧光光谱仪在培养的伊卡细胞和肌细胞中定量细胞内Ca 2+浓度（[Ca 2 +]（i））瞬变的活性。伊卡细胞产生自发的[Ca 2 +]i瞬变，消除河豚毒素或Ca 2 +-免费的解决方案，并显示大大降低幅度与L-型钙通道阻滞剂硝苯地平。[H-3]去甲肾上腺素研究证明了去甲肾上腺素的释放和摄取。伊卡细胞和共培养的心肌细胞产生的儿茶酚胺之间的功能相互作用通过β-肾上腺素能阻滞剂阿替洛尔引起搏动心肌细胞[Ca 2 +]（i）瞬变的幅度和频率的剂量依赖性降低的作用而明显。缺氧抑制伊卡细胞的[Ca 2 +] i瞬时活性，随后产生再氧介导的[Ca 2 +] i瞬时反弹增强。我们得出结论，伊卡细胞能够合成，释放和摄取儿茶酚胺。它们产生自发的[Ca 2 +] i瞬时活动，可以通过氧张力调节。伊卡细胞可能提供了一种替代肾上腺素供应，以维持心脏收缩和起搏功能，在休息和应激期间的交感神经支配的情况下。
Intrinsic cardiac adrenergic (ICA) cells in developing rat heart constitute a novel adrenergic signaling system involved in cardiac regulation. Regulatory mechanisms of ICA cells remain to be defined. Immunohistochemical study of fetal rat hearts demonstrated ICA cells with catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT). The mRNA of TH and PNMP was also detected in fetal rat hearts before sympathetic innervation. Immunoreactivity of norepinephrine transporter ( NET) was localized to ICA cells in rat heart tissue and primary cell culture. For the functional study, the activity of intracellular Ca2+ concentration ([Ca2+](i)) transients was quantified by a ratio fluorescent spectrometer in cultured ICA cells and myocytes. ICA cells generated spontaneous [Ca2+]i transients that were eliminated by tetrodotoxin or Ca2+-free solutions and showed greatly reduced amplitude with the addition of L-type Ca2+ channel blocker nifedipine. [H-3] norepinephrine studies demonstrate release and uptake of norepinephrine. Functional interaction between catecholamines produced by the ICA cells and cocultured myocytes was evident by the effect of the beta-adrenergic blocker atenolol eliciting a dose-dependent reduction in the amplitude and frequency of [Ca2+](i) transients of beating myocytes. Hypoxia inhibited [Ca2+](i) transient activity of ICA cells, which subsequently produced a reoxygenation-mediated rebound augmentation of [Ca2+] i transients. We conclude that ICA cells are capable of catecholamine synthesis, release, and uptake. They generate spontaneous [Ca2+] i transient activity that can be regulated by oxygen tension. ICA cells may provide an alternative adrenergic supply to maintain cardiac contractile and pacemaker function at rest and during stress in the absence of sympathetic innervation.