Three-dimensional analysis and molecular Mechanism of the autonomic nervous system in chronically hypoxic carotid body

颈动脉体是感受动脉血气和氢离子浓度变化的主要感觉器官，在慢性低、等和高碳酸血症缺氧大鼠中颈动脉体增大。在低、等二氧化碳缺氧时，VIP纤维密度明显增加，而NPY纤维密度无明显变化。高碳酸性缺氧时，NPY纤维密度明显增加，VIP纤维密度无明显变化。由于这些神经肽在性质上是血管活性的，改变颈动脉体循环可能有助于慢性缺氧对化学感受机制的调节。三维分析表明，这些肽能纤维主要与扩张的血管有关。此外，缺氧颈动脉体中的钙结合蛋白D-28 k纤维显著减少。慢性缺氧1个月后，颈动脉体缩小，NPY纤维密度增加，血管球细胞内[Ca^2+] i升高或降低。ACh和NaCN主要增加血管球细胞[Ca^2+] i，在去除Ca^2+后，这种[Ca^2 +] i反应的幅度维持在50%。在此基础上，我们提出了一个细胞内和细胞-纤维化学信号转导模型。相对大量的球细胞代表超极化，而少量的细胞代表去极化。缝隙连接和相互突触是血管球细胞和传入纤维之间相互作用的重要结构。有些传入神经纤维不产生放电，因为与它们的末梢并列的球细胞不脱髓鞘，而是过度增生。进一步的研究是必要的，以阐明触发化学转导机制。

The carotid bodies, which are the primary sensory organs for sensing changes in arterial blood gases and hydrogen ion concentration, were enlarged in the rat exposed to chronic hypo-, iso-, and hypercapnic hypoxia. In the hypo- and isocapnic hypoxia, the density of VIP fibers increased significantly, and the density of NPY fibers were unchanged. In the hypercapnic hypoxia, the density of NPY fibers was significantly increased, and that of VIP was unchanged. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia. Three-dimensional analysis showed that these peptidergic fibers are mainly associated with expanded vasculatures. In addition, calbindin D-28k fibers in the hypoxic carotid bodies was significantly decreased. The carotid body one month after the termination of chronic hypoxia was diminished in size, and the density of NPY fibers was increased.The hypoxia induced either an increase or a decrease in [Ca^<2+>] i in glomus cells. ACh and NaCN mostly increased in [Ca^<2+>] i in glomus cells, and maintained 50% of the amplitude of this [Ca^<2+>] response under the removal of Ca^<2+>. On the basis of these results, we proposed a model of intracellular and cell-to-fiber chemo-transduction in response to chemical stimuli. Relatively large number of glomus cells represent hyperpolarization, while a small number of cells represent depolarization. Gap junction and reciprocal synapses are depicted as important structures for interaction among glomus cells and afferent terminals. Some afferent nerve fibers produced no discharge, since the glomus cells apposed by their terminals do not depolarize, but rather hyperpolarize. A further study is necessary to elucidate what triggers chemo-transduction mechanism.