Comparative mechanisms of O2 and CO2/H+ sensing in vertebrates

被称为感觉受体的特殊细胞，使呼吸空气和水的动物能够察觉环境刺激的变化，并启动对生存至关重要的无意识反射反应。由于氧气（O2）对动物的生存至关重要，专门的O2受体有助于维持身体组织的最佳氧气供应。因此，当环境或血氧水平下降（缺氧）时，例如在高海拔地区，位于特定器官的O2受体细胞受到刺激。这些受体细胞通过向大脑中枢发送电信号来做出反应，从而触发呼吸的增加和血流的重新分配，以保护重要器官（例如大脑）。这些o2受体也可以检测血液中二氧化碳/氢离子的高水平。我们的长期目标是了解O2和CO2/H+水平是如何被感知的，感知机制是如何进化的，受体器官如何使用电信号和化学信号进行细胞间的相互作用和与大脑的交流，以及器官如何适应不同的缺氧模式。我们的大部分工作都集中在专门的哺乳动物“受体”器官上，即颈动脉体。此外，我们还广泛研究了另一个被称为肾上腺的器官，当动物暴露于缺氧等压力源时，肾上腺中含有释放重要“压力激素”的细胞；结果，动物变得更好地适应应付压力。基本的感知机制可能出现在水呼吸动物中，例如鱼类。在NSERC的资助下，我们首次在鱼鳃和哺乳动物颈动脉体中发现了类似的氧气感知机制。然而，我们最近的研究表明，颈动脉体中的信息处理更为复杂，因为涉及许多不同的神经化学物质和额外的细胞-细胞相互作用。这个NSERC应用程序的短期目标部分是了解大鼠颈动脉体细胞如何使用化学信号与彼此以及与神经系统进行交流。我们将使用玻璃电极来记录电活动，荧光染料来检测某些离子，药理和分子工具来确定这些化学物质的作用。此外，当动物（和人类）暴露于不同的缺氧模式时，颈动脉体和肾上腺功能也会发生变化。例如，长期缺氧（例如，高海拔或肺/心脏疾病）可导致颈动脉体敏感性和肾上腺释放的应激信号增加，这是有益的。然而，在呼吸紊乱时发生的间歇性缺氧（如睡眠呼吸暂停）可引起颈动脉体过度兴奋，导致高血压和心力衰竭。通过研究神经化学物质、受体蛋白、细胞相互作用和电信号对颈动脉和肾上腺功能的影响，我们希望对它们在正常和异常呼吸和心血管生理中的作用提供新的信息。

Specialized cells, known as sensory receptors, allow air- and water-breathing animals to detect changes in environmental stimuli, and initiate unconscious reflex responses crucial for survival. Since oxygen (O2) is essential for animal survival, specialized O2-receptors help maintain an optimal supply of O2 to the body tissues. Thus, when environmental or blood O2 levels fall (hypoxia), e.g. at high altitude, O2-receptor cells located in specific organs are stimulated. These receptor cells respond by sending electrical signals to brain centers that trigger an increase in breathing and a redistribution of blood flow to protect vital organs (e.g. the brain). These O2-receptors can also detect high CO2 /H+ levels in blood. Our long-term goals are to understand how O2 and CO2/H+ levels are sensed, how the sensing mechanisms have evolved, how receptor organs use electrical and chemical signals for cell-cell interactions and communication with the brain, and how the organs adapt to different patterns of hypoxia. Most of our work has focused on specialized mammalian ‘receptor’ organs, known as carotid bodies. Also, we studied extensively another organ known as the adrenal gland, which contains cells that release important ‘stress hormones’ when animals are exposed to stressors such as hypoxia; as a result the animal becomes better adapted to cope with the stress. The basic sensing mechanisms probably arose in water-breathing animals, e.g. fish, and with NSERC funding, we were the first to show similar O2 sensing mechanisms in fish gills and mammalian carotid body. However, our recent studies suggest that information processing in the carotid body is more complex, as many different neurochemicals and additional cell-cell interactions are involved. The short-term goals of this NSERC application are partly to understand how rat carotid body cells use chemical signals to communicate with each other and with the nervous system. We will use glass electrodes to record electrical activity, fluorescent dyes to detect certain ions, pharmacological and molecular tools to determine how these chemicals act. Moreover, changes in carotid body and adrenal gland functions occur when animals (and humans) are exposed to different patterns of hypoxia. For example, long-term hypoxia (e.g. high altitude or lung/heart disease) can lead to an increase in both carotid body sensitivity and stress signals released from the adrenal gland which have beneficial effects. However, intermittent hypoxia as occurs during disordered breathing (e.g. sleep apnea) can cause over-excitation of the carotid body, leading to hypertension and heart failure. By studying how neurochemicals, receptor proteins, cell interactions, and electrical signals contribute to carotid body and adrenal gland function we expect to contribute novel information about their roles in both normal & abnormal respiratory and cardiovascular physiology.