Leonard Erin M, Salman Shaima, Nurse Colin A
Department of Biology, McMaster University, Hamilton, ON, Canada.
Front Physiol. 2018 Mar 16;9:225. doi: 10.3389/fphys.2018.00225. eCollection 2018.
Maintenance of homeostasis in the respiratory and cardiovascular systems depends on reflexes that are initiated at specialized peripheral chemoreceptors that sense changes in the chemical composition of arterial blood. In mammals, the bilaterally-paired carotid bodies (CBs) are the main peripheral chemoreceptor organs that are richly vascularized and are strategically located at the carotid bifurcation. The CBs contribute to the maintenance of O, CO/H, and glucose homeostasis and have attracted much clinical interest because hyperactivity in these organs is associated with several pathophysiological conditions including sleep apnea, obstructive lung disease, heart failure, hypertension, and diabetes. In response to a decrease in O availability (hypoxia) and elevated CO/H (acid hypercapnia), CB receptor type I (glomus) cells depolarize and release neurotransmitters that stimulate apposed chemoafferent nerve fibers. The central projections of those fibers in turn activate cardiorespiratory centers in the brainstem, leading to an increase in ventilation and sympathetic drive that helps restore blood PO and protect vital organs, e.g., the brain. Significant progress has been made in understanding how neurochemicals released from type I cells such as ATP, adenosine, dopamine, 5-HT, ACh, and angiotensin II help shape the CB afferent discharge during both normal and pathophysiological conditions. However, type I cells typically occur in clusters and in addition to their sensory innervation are ensheathed by the processes of neighboring glial-like, sustentacular type II cells. This morphological arrangement is reminiscent of a "tripartite synapse" and emerging evidence suggests that paracrine stimulation of type II cells by a variety of CB neurochemicals may trigger the release of "gliotransmitters" such as ATP via pannexin-1 channels. Further, recent data suggest novel mechanisms by which dopamine, acting via D2 receptors (D2R), may inhibit action potential firing at petrosal nerve endings. This review will update current ideas concerning the presynaptic and postsynaptic mechanisms that underlie chemosensory processing in the CB. Paracrine signaling pathways will be highlighted, and particularly those that allow the glial-like type II cells to participate in the integrated sensory response during exposures to chemostimuli, including acute and chronic hypoxia.
呼吸和心血管系统内稳态的维持依赖于一些反射，这些反射始于专门的外周化学感受器，这些感受器能感知动脉血化学成分的变化。在哺乳动物中，双侧成对的颈动脉体（CBs）是主要的外周化学感受器器官，血管丰富，位于颈动脉分叉处，位置关键。颈动脉体有助于维持氧气、二氧化碳/氢离子和葡萄糖的内稳态，并引起了众多临床关注，因为这些器官的功能亢进与多种病理生理状况相关，包括睡眠呼吸暂停、阻塞性肺病、心力衰竭、高血压和糖尿病。响应于氧气供应减少（低氧）和二氧化碳/氢离子升高（酸性高碳酸血症），CB I型（球样）细胞去极化并释放神经递质，刺激相邻的化学传入神经纤维。这些纤维的中枢投射继而激活脑干中的心肺中枢，导致通气增加和交感神经驱动增强，有助于恢复血液中的氧分压并保护重要器官，如大脑。在理解诸如ATP、腺苷、多巴胺、5-羟色胺、乙酰胆碱和血管紧张素II等I型细胞释放的神经化学物质如何在正常和病理生理状况下塑造CB传入放电方面已取得重大进展。然而，I型细胞通常成簇出现，除了接受感觉神经支配外，还被相邻的神经胶质样、支持性II型细胞的突起所包裹。这种形态学排列让人联想到“三联突触”，新出现的证据表明，多种CB神经化学物质对II型细胞的旁分泌刺激可能通过pannexin-1通道触发“胶质递质”如ATP的释放。此外，最近的数据表明了新的机制，即多巴胺通过D2受体（D2R）发挥作用，可能抑制岩神经末梢的动作电位发放。本综述将更新有关CB化学感受处理基础的突触前和突触后机制的当前观点。将突出旁分泌信号通路，特别是那些使神经胶质样II型细胞在暴露于化学刺激物（包括急性和慢性低氧）期间参与综合感觉反应的信号通路。
