MODULATION OF CHEMICAL TRANSMISSION IN SENSORY RECEPTORS

颈动脉体是对O2敏感的动脉化学感受器， CO2，拥有专门的前神经I型细胞， 神经递质 目前的观点认为， 化学感受器刺激启动复杂的级联转导事件 在这些细胞中，兴奋性递质的释放达到高潮 激活颈动脉的紧密并列感觉纤维的试剂 窦神经（CSN）。 大量的生物物理和神经化学研究 部分阐明了化学转导的机制， 化学传递 然而，它已变得越来越 显然，I型细胞/感觉神经的化学敏感性 结束复合体是由强大的外在机制， 这种受体复合物的直接神经支配， 内在的细胞机制，由化学刺激触发， 器官。 直接神经元控制包括1），一个未识别的神经元 抑制成分在CSN中行进，和2）交感神经纤维在CSN中行进， 神经节球神经（GGN）接触I型细胞，但其 功能也同样没有特征。 同样定义不清的还有 化学刺激可以激发的内在细胞机制 受体复合物发生了巨大变化，包括I型细胞 肥大、增生和神经递质水平改变， 化学感受器阈值 这里的实验将使用 多学科的方法来研究这些神经和细胞 化学感受器调节的机制。 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 电生理技术来阐明两个假定的 抑制剂，一氧化氮和心房利钠肽， 化学感受器活性的调节。 2)化学感受器研究 交感神经支配的调制将使用独特的体外 灌流室，以评估直接节前与节后 对I型细胞和CSN活性的影响。 3)最后，影响 化学刺激和慢性去神经支配对细胞/分子过程的影响 在I型细胞中，将在旨在研究 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， 杂交技术 这些研究的最终目的是 阐明突触和细胞过程，这是关键， 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.