Oxygen chemoreceptors in aquatic vertebrates

控制氧摄取对于所有脊椎动物在低氧（缺氧）期间的生存都很重要。专门的细胞，称为氧化学感受器，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生理变化。虽然许多研究已经描述了哺乳动物中的这些细胞，但在水生脊椎动物（如鱼类和两栖动物）中，氧化学感受器的定义很差。这项发现补助金申请提出了填补这些空白的研究，并：（i）确定膜离子通道和细胞内因子在“塑造”斑马鱼和金鱼对缺氧的氧化学感受器反应中的作用，（ii）使用新的实验方法研究鳃中化学感受器和感觉神经元之间的突触生理学，和（iii）在细胞水平上表征皮肤氧化学感受器的第一生理反应。拟议的实验将包括敏感的膜片钳电生理记录和分离的化学感受器，高分辨率共聚焦显微镜和行为研究的显微荧光光谱。这项研究将首次描述鳃中氧感应的细胞和神经化学基础，以及这些过程从胚胎到成体的发展。这项研究也将提供一个更好的了解呼吸调节可能已经演变。这些发现将构成氧传感，神经生物学，发育和比较生理学领域的重大进展。该计划将支持平均每年4名硕士或博士研究生的培训。此外，还有众多的本科生。

The control of oxygen uptake is important to all vertebrates for survival during periods of low oxygen (hypoxia). Specialized cells, called oxygen chemoreceptors, detect changes in blood or environmental oxygen and initiate a cascade of events that ultimately leads to physiological changes in respiratory rate and cardiovascular function. While many studies have described these cells in mammals, oxygen chemoreceptors are poorly defined in aquatic vertebrates, such as fish and amphibians. This Discovery Grant application proposes research to fill these voids and: (i) determine the role of membrane ion channels and intracellular factors in 'shaping' the oxygen chemoreceptor response to hypoxia in zebrafish and goldfish, (ii) study the synaptic physiology between chemoreceptors and sensory neurons in the gill using a novel experimental approach, and (iii) characterize the first physiological response of a skin oxygen chemoreceptor at the cellular level. The proposed experiments will include sensitive patch-clamp electrophysiological recording and microspectrofluorimetry of isolated chemoreceptors, high-resolution confocal microscopy, and behavioural studies. This research will provide the first description of the cellular and neurochemical basis of oxygen sensing in the gill, and the development of these processes from embryos to adults. 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, development and comparative physiology. The program will support the training of an average of 4 graduate students per year at the M.Sc. or Ph.D. level, in addition to numerous undergraduate students.