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

被称为感觉受体的特殊细胞允许呼吸空气和水的动物检测环境刺激的变化，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O2供应。因此，当环境或血液中的O2水平下降(低氧)时，例如在高海拔地区，位于特定器官的O2受体细胞被刺激。这些受体细胞通过向大脑中心发送电信号来做出反应，从而触发呼吸增加和血流量重新分配，以保护重要器官(例如大脑)。这些O2-受体还可以检测到血液中高水平的二氧化碳/氢。我们的长期目标是了解O2和CO2/H水平是如何被感知的，感知机制是如何演变的，受体器官如何使用电子和化学信号进行细胞与细胞之间的相互作用和与大脑的沟通，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哺乳动物的特殊“受体”器官上，也就是众所周知的颈动脉小体。此外，我们还对另一个被称为肾上腺的器官进行了广泛的研究，肾上腺含有细胞，当动物暴露在缺氧等应激因素下时，肾上腺细胞会释放重要的应激激素；结果是，动物变得更好地适应了压力。基本的感知机制可能出现在呼吸水的动物中，例如鱼类，在NSERC的资助下，我们第一个在鱼类的鳃和哺乳动物的颈动脉小体中展示了类似的氧气感知机制。然而，我们最近的研究表明，颈动脉小体的信息处理更加复杂，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。NSERC应用程序的短期目标部分是为了了解大鼠颈动脉小体细胞如何使用化学信号相互通信以及与神经系统进行通信。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，药理学和分子工具来确定这些化学物质是如何作用的。此外，当动物(和人类)暴露在不同的缺氧模式下时，颈动脉体部和肾上腺功能会发生变化。例如，长期低氧(如高原或肺/心脏病)可导致颈动脉体敏感度和肾上腺释放的压力信号增加，这具有有益的影响。然而，在呼吸紊乱(如睡眠呼吸暂停)期间发生的间歇性低氧会导致颈动脉体过度兴奋，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体部和肾上腺功能的影响，我们期望对它们在正常和异常呼吸系统和心血管生理学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.