CAROTID BODY CHEMOTRANSDUCTION& CARDIOPULMONARY CONTROL

颈动脉小体在许多心血管疾病中起着重要作用， 对低氧、高碳酸血症和酸中毒的呼吸和内分泌反应。 然而，动脉低氧转化的机制， 高碳酸血症或酸中毒导致颈动脉小体神经活动增强 只是知之甚少。颈动脉小体的形态， 颈动脉I型细胞中几种神经递质的存在 身体，以及最近在I型细胞中的电生理发现表明 化学转导可以合理地模仿神经节细胞 变速箱。含有神经递质的I型细胞类似于 突触前神经元与I型细胞相对的神经元相似 到突触后神经元。这样做的广泛、长期目标是 提案的目的是探索这一过程的各个组成部分和关系 模特。总体假设是低氧、高碳酸血症或酸中毒。 为了使I型电池去极化，允许激活电压门控 钙通道(VGCC)与随后释放的神经递质 这些细胞。这项提案的具体目标集中在 I型细胞在低氧期间神经活动增强的发生中， 高碳酸血症和酸中毒。具体目标有三：(一)确定 I型细胞的电活动及其对其的影响 低氧、高碳酸血症和酸中毒；(2)确定是否存在 VGCC亚型(T、L、N)在I型细胞和 它们在上述自然刺激中的化学转导作用；(3) 确定CO_2/HCO_3系统在神经活动发生中的作用 在自然刺激的化学转导过程中。这些目标将是 研究对象：(1)在全动物实验中，颈动脉小体 在原位有选择地间歇地灌流各种溶液 同时记录颈动脉窦神经活动；(2)新鲜分离或 含特定离子的颈动脉体I型细胞短期培养 使用膜片钳记录电导和膜电位 技术。I型细胞的细胞内游离钙和pH值也是 用荧光染料测量。我们的初步数据显示，VGCC 在低氧和高二氧化碳的化学转导中起关键作用，而 CO_2/HCO_3的存在对低氧和 酸中毒。提案有意识地试图利用 体外实验，以加深对实验结果的理解 活体实验。这些来自成人的结果可以作为基准 在胎儿、新生儿和发育中的动物中进行类似的研究 颈动脉体对心肺控制的影响甚至更大 对上呼吸道的肌肉进行显著的控制。是这样的 研究直接与婴儿猝死综合症和 呼吸不稳定在新生儿中非常普遍。

The carotid body plays an important role in many of the cardiovascular, respiratory, and endocrine responses to hypoxia, hypercapnia and acidosis. However, the mechanisms responsible for the conversion of arterial hypoxia, hypercapnia, or acidosis into increased neural activity in the carotid body are only poorly understood. The morphology of the carotid body, the presence of several neurotransmitters in the Type I cells of the carotid body, and recent electrophysiological findings in the Type I cells suggest that chemotransduction can be reasonably modelled after ganglionic transmission. The neurotransmitter-containing Type I cell is analogous to the presynaptic neuron while the neuron apposed to Type I cell is analogous to the postsynaptic neuron. The broad, long-term objective of this proposal is to explore the various components and relationships of this model. The overall hypothesis calls for hypoxia, hypercapnia, or acidosis to depolarize the Type I cells, allowing an activation of voltage-gated calcium channels (VGCC) with subsequent release of neurotransmitters from these cells. The specific aims of this proposal focus on the role of the Type I cells in the genesis of increased neural activity during hypoxia, hypercapnia, and acidosis. The specific aims are three: (1) To determine the electrical activity of Type I cells and how it is influenced by hypoxia, hypercapnia, and acidosis; (2) To determine the presence and characteristics of the subtypes of VGCC (T, L, N) in the Type I cell and their role in chemotransduction during the above natural stimuli; (3) To determine the role of the CO2/HCO3 system in the genesis of neural activity during the chemotransduction of natural stimuli. These aims will be pursued: (1) in whole animals experiments in which the carotid body in situ is selectively and intermittently perfused with various solutions while recording carotid sinus nerve activity; (2) in freshly dissociated or short-term cultured carotid body Type I cells in which specific ion conductances and membrane potentials are recorded using the patch clamp technique. Intracellular free calcium and pH of the Type I cells are also measured using fluorescent dyes. Our preliminary data suggest that VGCC play a key role for hypoxic and hypercapnic chemotransduction, and that the presence of CO2/HCO3 is essential for chemotransduction of hypoxia and acidosis. The proposal consciously attempts to utilize the results of the in vitro experiments to give a deepened understanding to the results of the in vivo experiments. These results from the adult can serve as a benchmark for similar studies in the fetus, newborn, and developing animal where the carotid body influences cardiopulmonary control even more strongly and exercises significant control over the muscles of the upper airways. Such studies pertain directly to Sudden Infant Death Syndrome and to the respiratory instability so prevalent in the newborn.