RUI: Comparative Hypoxic Chemosensitivity of Two Rat Strains

动物对低氧环境的反应是增加呼吸。这种呼吸的增加是由称为颈动脉体的结构中的氧敏感细胞刺激的。关于颈动脉体细胞如何将血液中的低氧水平（缺氧）信号转化为导致呼吸增加的大脑神经信号，有许多理论，但哪种理论是正确的仍然没有解决。氧气通过存在于红细胞中的血红蛋白携带在血液中。血红蛋白是一种所谓的“血红素”蛋白，在体内的其他细胞中也有其他血红素蛋白。关于颈动脉体细胞如何感知氧气水平变化的理论之一是通过血红素蛋白，该血红素蛋白可以在细胞内或细胞膜上结合氧气。 对几种哺乳动物、鸟类甚至一些爬行动物的比较研究表明，血红蛋白对氧的亲和力（或血红蛋白结合氧的容易程度）与刺激呼吸增加所需的血液中氧含量下降之间存在良好的相关性。该观察结果的潜在机制可能是结合血液中氧的b型血红素蛋白和结合颈动脉体的氧敏感细胞中氧的b型血红素蛋白的氧结合特性的匹配或共性。如果是这样的话，该机制不仅有助于阐明颈动脉体如何工作，而且还有助于阐明呼吸控制如何演变为与血液的氧气运输特性相匹配。为了进一步探索这一概念，本项目将研究两种大鼠，它们对氧气减少或缺氧表现出不同的呼吸和代谢反应。将确定它们的血红蛋白的结合特性以查看它们是否不同，并且将测量它们的颈动脉体对缺氧的响应特性或敏感性以确定整个动物在呼吸和代谢方面的缺氧敏感性的差异是否可以与颈动脉体的缺氧敏感性的差异相关。如果它们是相关的，那么将来将进行颈动脉体和氧敏感离子通道中血红素蛋白的比较研究。如果不是，那么将追求关于控制不同缺氧敏感性的机制的替代假设。

Animals respond to environments that are low in oxygen by increasing their breathing. This increase in breathing is stimulated by oxygen sensitive cells in a structure called the carotid body. There are a number of theories about how the carotid body cells can transduce the signal of low oxygen levels (hypoxia) in the blood into nerve signals to the brain that cause the increase in breathing, but which theory is correct remains unresolved. Oxygen is carried in the blood on hemoglobin that is present in red blood cells. Hemoglobin is a so-called 'heme'-protein and there are other heme-proteins in other cells in the body. One of the theories about how carotid body cells sense changes in oxygen levels is via a heme-protein that can bind oxygen either inside the cell or at its membrane. Comparative studies of several species of mammals, birds and even some reptiles have demonstrated a good correlation between the affinity of hemoglobin for oxygen, or the ease with which hemoglobin binds oxygen, and the amount of decline in oxygen in the blood required to stimulate an increase in breathing. The mechanism underlying this observation may be a matching or commonality of oxygen binding characteristics of the b-type heme protein binding oxygen in the blood and a b-type heme protein binding oxygen in the oxygen sensitive cells of the carotid bodies. If this is the case, the mechanism may help elucidate not only how the carotid bodies work but how the control of breathing has evolved to be well matched to the oxygen transport properties of the blood. To explore this concept further this project will investigate two strains of rats that exhibit different breathing and metabolic responses to reduced oxygen or hypoxia. The binding characteristics of their hemoglobin will be determined to see if they differ, and the response characteristics, or sensitivity, of their carotid bodies to hypoxia will be measured to determine whether or not the differences in hypoxic sensitivity of the whole animal, in terms of breathing and metabolism, can be related to differences in the hypoxic sensitivity of the carotid body. If they are related, then future comparative studies of heme-proteins in the carotid bodies and oxygen sensitive ion channels will be conducted. If not, then alternative hypotheses about the mechanisms controlling the different hypoxic sensitivities will be pursued.