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、生理性变化。尽管许多研究已经使用哺乳动物模型解决了这些问题，但许多问题和争议仍然围绕着氧化学接收的细胞机制。而这些过程在水生脊椎动物中的定义很差。这项发现拨款申请提出了一项研究，以填补这些空白：(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方面的生理作用(S)，(Ii)表征对氧敏感的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年的发展。*拟议的实验将在有鳃的水生脊椎动物上进行，如斑马鱼、金鱼、和两栖幼虫。新的实验技术将包括敏感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的变化，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气感应的细胞和神经化学基础，以及这些过程的发展。这项研究还将提供对呼吸调节可能如何进化的更多了解。尽管这些发现将构成氧气感应领域的重大进展，神经生物学和比较生理学。建议的项目将支持M.SC平均每年培养3名研究生。或者博士学位。

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.