CAROTID BODY CHEMOTRANSDUCTION & CARDIOPULMONARY CONTROL

颈动脉体在许多心血管疾病中起重要作用， 呼吸和内分泌对缺氧、高碳酸血症和酸中毒的反应。 然而，负责动脉缺氧转换的机制， 高碳酸血症，或酸中毒到颈动脉体神经活动增加 我们对此知之甚少 颈动脉体的形态， 颈动脉I型细胞中存在几种神经递质 身体，和最近的电生理研究结果在I型细胞表明， 化学转导可以合理地模拟神经节后， 传输 含有神经递质的I型细胞类似于 突触前神经元与I型细胞并列的神经元类似 突触后神经元 这一广泛而长期的目标 建议是探讨这一问题的各种组成部分和关系， 模型 总的假设是缺氧、高碳酸血症或酸中毒 去活化I型细胞，允许激活电压门控的 钙通道（VGCC），随后释放神经递质 这些细胞。 本提案的具体目标侧重于 I型细胞在缺氧时神经活动增加的发生中， 高碳酸血症和酸中毒 具体目标有三：（1）确定 I型细胞的电活动以及它如何受到 缺氧、高碳酸血症和酸中毒;（2）确定是否存在和 I型细胞中VGCC亚型（T，L，N）的特征， 它们在上述自然刺激过程中的化学转导中的作用;（3） 确定CO2/HCO 3系统在神经活动发生中的作用 在自然刺激的化学传导过程中。 这些目标将是 （1）在整个动物实验中， 用各种溶液选择性地和间歇性地灌注原位 同时记录颈动脉窦神经活动;（2）在新鲜分离或 短期培养的颈动脉体I型细胞，其中特定离子 使用膜片钳记录电导和膜电位 法 I型细胞的细胞内游离钙和pH也是 使用荧光染料测量。 我们的初步数据表明，VGCC 在低氧和高碳酸化学转导中起关键作用， CO2/HCO 3的存在对于低氧的化学转导是必需的， 酸中毒 该提案有意识地试图利用 体外实验，以加深对 体内实验。 这些成年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更大， 对上呼吸道的肌肉有很强的控制力。 等 研究直接涉及婴儿猝死综合症和 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.