Three-dimensional analysis and molecular mechanism of the peptidergic innervation in the arterial chemoreceptor organ

颈动脉小体是感受动脉血气和氢离子浓度变化的主要感觉器官，在慢性等颅压低氧(10%O2和3-4%CO2，持续3个月)中，颈动脉小体增大。扩大的颈动脉小体的肽能神经支配与正常氧对照的颈动脉小体不同。慢性缺氧性颈动脉体内P物质和降钙素基因相关肽纤维密度显著降低至50%以下，血管活性肠肽纤维密度显著增加1.80倍，神经肽Y纤维密度不变。三维分析表明，这些肽能纤维主要与扩张的血管有关。此外，缺氧性颈动脉小体内含一氧化氮合酶的神经纤维密度明显降低。这些形态结果表明，慢性低氧颈动脉小体神经支配的改变是低氧适应的特征之一。由于这些神经肽在本质上是血管活性的，改变颈动脉体循环可能有助于慢性低氧对化学感觉机制的调节，而且由于人们认为一氧化氮(NO)是正常缺氧颈动脉小体中的抑制性神经元信使，目前的发现表明，低氧颈动脉小体的感觉机制可能涉及由于NO合成减少而导致的“去抑制”。低氧和化学刺激增加了球体细胞(化学感受器细胞)内的钙离子，但不增加簇中约20%的球体细胞内的钙离子。这些生理结果提示，细胞内游离钙离子可能是由细胞内钙离子结合产生的，细胞内钙离子浓度升高可能通过激活钙依赖的钾通道而发生超极化。

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 isocapnic hypoxia (10% 02 in N2 and 3-4% C02 for 3 months). The peptidergic innervation in the enlarged carotid bodies was different from that in the normoxic control carotid bodies. The density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50 %, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Three-dimensional analysis showed that these peptidergic fibers are mainly associated with expanded vasculatures. In addition, the density of NOS-containing nerve fibers in the hypoxic carotid bodies was significantly decreased. These morphological results suggest that altered innervation of the chronica1ly hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia, and because it has been considered that nitric oxide (NO) is an inhibitory neuronal messenger in the normoxic carotid body, the present findings suggest that the sensory mechanisms in the hypoxic carotid body may be involved in 'disinhibition' resulting from reduced NO synthesis.Hypoxic and chemical stimuli increased intracellular Ca^<2+> in the glomus cells (chemoreceptor cells), but did not increase intracellular Ca^<2+> in about 20% of glomus cells in the cluster. These physiological results suggest that free Ca^<2+> may be produced from intracellular binding Ca^<2+> in response to the stimuli, and also that glomus cells with increased intracellular Ca^<2+> may hyperpolarize through the activation of calcium-dependent potassium channels.