Comparative study of oxygen sensing in adult and developing vertebrates

控制摄氧量对所有脊椎动物的生存和适应新环境都很重要。被称为氧化学感受器的特殊细胞检测血液或环境中氧的变化，并启动一系列事件，最终导致呼吸频率和心血管功能的适应性生理变化。虽然许多研究已经使用哺乳动物模型解决了这些问题，但围绕氧气化学接受的细胞机制仍然存在许多问题和争议，并且这些过程在水生脊椎动物中定义不清。这项发现基金申请提出了填补这些空白的研究，并：(i)确定化学感受器膜离子通道在将低氧刺激转化为有意义的细胞信号中的生理作用，（ii）表征氧敏感化学感受器和感觉神经元之间通信的化学和功能基础，以及（iii）研究这些过程从胚胎到成人的发展。拟议的实验将在有鳃的水生脊椎动物上进行，例如斑马鱼、金鱼和两栖动物的幼虫。实验技术将包括灵敏的膜片钳记录分离的化学感受器和感觉神经元，以检测通过膜离子通道的电流变化，以及高分辨率共聚焦显微镜。预计这项研究将首次描述水生脊椎动物氧感知的细胞和神经化学基础，以及这些过程的发展。这项研究也将提供对呼吸调节如何进化的更好理解。这些发现将构成氧传感、神经生物学和比较生理学领域的重大进展。该计划将支持平均每年培养3名硕士或博士研究生。

The control of oxygen uptake is important to all vertebrates for survival and adaptation to new environments.  Specialized cells, called oxygen chemoreceptors, detect changes in blood or environmental oxygen and initiate a cascade of events that ultimately lead to adaptive, physiological changes in respiratory rate and cardiovascular function.  While many studies have addressed these issues using mammalian models, many questions and controversies still surround the cellular mechanisms of oxygen chemoreception, and these processes are poorly defined in aquatic vertebrates.  This Discovery Grant application proposes research to fill these voids and: (i) identify the physiological role(s) of chemoreceptor membrane ion channels in converting a low-oxygen stimulus into a meaningful cellular signal, (ii) characterize the chemical and functional basis of communication between oxygen-sensitive chemoreceptors and sensory neurons, and (iii) study the development of these processes from embryo to adult.  The proposed experiments will be performed on aquatic vertebrates that bear gills, e.g. zebrafish, goldfish, and amphibian larvae.  Experimental techniques will include sensitive patch-clamp recording of isolated chemoreceptors and sensory neurons to detect changes in electrical current through membrane ion channels, and high-resolution confocal microscopy.  It is anticipated that this research will provide the first description of the cellular and neurochemical basis of oxygen sensing, and the development of these processes, in aquatic vertebrates.  This research will also provide a greater understanding of how respiratory regulation may have evolved.  These findings will constitute significant advances in the fields of oxygen sensing, neurobiology and comparative physiology.  The proposed program will support the training of an average of 3 graduate students per year at the M.Sc. or Ph.D. level.