MODULATION OF CHEMICAL TRANSMISSION IN SENSORY RECEPTORS

颈动脉小体是动脉化学感受器，对O2和 二氧化碳，拥有含有阵列的专门的前神经类型I细胞 神经递质毒剂。目前的观点认为，这种风险敞口 化学感受器刺激启动一系列复杂的传导事件 在这些细胞中，最终释放兴奋性递质 激活颈动脉紧密相对感觉纤维的药剂(S) 窦神经(CSN)。大量的生物物理和神经化学研究 已经部分阐明了化学转导和 在这个器官中的化学传播。然而，它已经变得越来越多 显然，I型细胞/感觉神经的化疗敏感性 结束复合体受到强大的外部机制的调节，包括 这种受体复合体的直接神经支配，并通过重要的 由化学刺激触发的内在细胞机制 管风琴。直接神经控制包括1)，一种未知的神经 在CSN中移动的抑制成分，以及2)交感神经纤维在 神经节球神经(GGN)与I型细胞接触，但其 功能同样是非特色化的。同样定义模糊的还有 化学刺激可引发的内在细胞机制 受体复合体的戏剧性变化，包括I型细胞 肥大、增生和神经递质水平改变以及 化学感受阈值。这里制定的实验将使用 用多学科方法研究这些神经和细胞 化学感受器的调节机制。我们的研究计划包括 三个具体目标：1)我们将识别神经元和 参与化学感受器抑制的神经递质机制 CSN.这些实验利用免疫细胞化学、神经化学和 电生理学技术阐明两种推定的 抑制药，一氧化氮和心钠素，在 化学感受器活性的调节。2)化学感受器的研究 交感神经的调制将在体外使用一种独特的 灌流室评估直接节前与节后的对比 对I型细胞和CSN活性的影响。3)最后， 化学刺激和慢性失神经对细胞/分子过程的影响 将在旨在研究I型细胞的实验中进行评估 基因表达在化学反应调节中的作用。这些 实验涉及使用现代基因扩增和 杂交技术。这些研究的最终目的是 阐明突触和细胞过程是 与自然刺激相关的化学感受器适应。

The carotid body, an arterial chemoreceptor organ sensitive to O2 and CO2, possesses specialized pre-neural type I cells which contain an array of neurotransmitter agents. Current views hold that exposure to chemoreceptor stimuli initiates a complex cascade of transductive events in these cells, culminating in the release of excitatory transmitter agent(s) which activate closely apposed sensory fibers of the carotid sinus nerve (CSN). Numerous biophysical and neurochemical investigations have partially elucidated the mechanisms underlying chemotransduction and chemotransmission in this organ. However, it has become increasingly apparent that the chemosensitivity of the type I cell/sensory nerve ending complex is modulated by powerful extrinsic mechanisms involving direct neural innervation of this receptor complex, and by important intrinsic cellular mechanisms which are triggered by chemostimulation of the organ. Direct neural control consists of 1), an unidentified neural inhibitory component traveling in the CSN, and 2), sympathetic fibers in the gangliomerular nerve (GGN) which contact type I cells but whose function is likewise uncharacterized. Equally ill-defined are the intrinsic cellular mechanisms by which chemostimulation can invoke dramatic changes in the receptor complex, including type I cell hypertrophy, hyperplasia, and altered neurotransmitter levels and chemoreceptor thresholds. The experiments formulated here will use a multidisciplinary approach to investigate these neural and cellular mechanisms of chemoreceptor modulation. Our research plan consists of three specific aims: 1) we will identify the neurons and the neurotransmitter mechanisms involved in chemoreceptor inhibition via the CSN. These experiments utilize immunocytochemical, neurochemical and electrophysiological techniques to elucidate the roles of two putative inhibitory agents, nitric oxide and atrial natriuretic peptide, in modulation of chemoreceptor activity. 2) Studies of chemoreceptor modulation by the sympathetic innervation will use a unique in vitro superfusion chamber to assess direct preganglionic vs. postganglionic effects on type I cells and CSN activity. 3) Finally, the effects of chemostimulation and chronic denervation on cellular/molecular processes in type I cells will be evaluated in experiments designed to study the role of gene expression in regulation of the chemoresponse. These experiments involve the use of modern gene amplification and hybridization techniques. The ultimate aim of these studies is to clarify the synaptic and cellular processes which are key to chemoreceptor adaptations associated with natural stimulation.