Control of Breathing in Vertebrates

脊椎动物呼吸的控制

• 批准号: RGPIN-2022-03140
• 负责人: Milsom, William
• 金额: $ 5.68万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=766133
• 关键词: Control; Breathing; Vertebrates

An adequate supply of oxygen is important for the survival of all tissues in all vertebrates but is especially critical for tissues with high energy demands such as heart and brain. Hypoxic stress (low oxygen) (environmentally induced such as at altitude, in burrows and in O2 poor waters, or metabolically induced such as by exercise, digestion and reproduction) has driven the evolution of novel adaptations in animals that encounter such conditions. The key to tolerating hypoxia is to match O2 supply to O2 demand. The first step in the process of regulating O2 supply, is ventilation, and one goal of my research program is to determine why animals breathe the way they do under different conditions (at rest, sleep, exercise, altitude, dormancy, hibernation, diving, etc.). Breathing is essential for gas exchange in all large, multicellular organisms, but the mechanistic basis of respiratory rhythm generation and the manner in which the basic rhythm is modified to meet changing demands are not fully understood. We also don't fully understand how the other steps in the gas transport cascade that move O2 and CO2 between the atmosphere and the mitochondria are regulated and integrated to meet fluctuating demands in different environments. These steps include the diffusion of gases across the gills/lungs, the transport of O2 in the blood by the pumping of the heart, the capacity of blood to hold O2, and the diffusion of O2 from the blood into the tissues. All of these steps are modulated by the interaction of peripheral sensory feedback and such descending inputs as those associated with locomotion, changes in arousal state (such as sleep, dormancy and hibernation) and body temperature. By investigating the mechanistic basis of the regulatory steps in this cascade, our work provides insight into the developmental (phenotypic) and evolutionary (genotypic) plasticity of one of the most essential process for life; gas exchange. There is also another side to this equation. Matching oxygen supply and demand can be met under hypoxic conditions not only by increasing supply but also by suppressing demand. The mechanistic basis of hypoxic metabolic suppression and the manner in which it is modified in the face of changing oxygen supply are even less well understood, as is the manner in which the balance between increasing supply versus reducing demand is orchestrated. Using species differences (phylogeny), developmental changes (ontogeny) and genetic manipulations as tools, my students and I hope to determine the ways in which the mechanisms matching metabolic supply and demand have been shaped by evolution to meet the demands of vertebrates with varied life histories living in different environments.

充足的氧气供应对所有脊椎动物的所有组织的生存都很重要，但对心脏和大脑等高能量需求的组织尤为重要。低氧应激（低氧）（环境诱导的，例如在海拔、洞穴和贫O2沃茨中，或代谢诱导的，例如通过运动、消化和繁殖）驱动了遇到这种条件的动物的新适应的进化。耐受缺氧的关键是使O2供应与O2需求相匹配。调节氧气供应的第一步是通风，我的研究计划的一个目标是确定为什么动物在不同条件下（休息，睡眠，运动，海拔，休眠，冬眠，潜水等）呼吸的方式。呼吸对于所有大型多细胞生物体的气体交换都是必不可少的，但呼吸节律产生的机制基础以及基本节律被修改以满足不断变化的需求的方式尚未完全理解。我们也不完全了解在大气和线粒体之间移动O2和CO2的气体运输级联中的其他步骤是如何调节和整合的，以满足不同环境中波动的需求。这些步骤包括气体穿过鳃/肺的扩散、通过心脏的泵送在血液中运输O2、血液保持O2的能力以及O2从血液扩散到组织中。所有这些步骤都受到外周感觉反馈和下行输入（如与运动、唤醒状态（如睡眠、休眠和冬眠）和体温变化相关的输入）的相互作用的调节。通过研究这一级联中的调节步骤的机制基础，我们的工作提供了对生命最基本过程之一的发育（表型）和进化（基因型）可塑性的洞察;气体交换。这个等式还有另一面。在低氧条件下，不仅可以通过增加供应，而且可以通过抑制需求来满足匹配的氧气供应和需求。低氧代谢抑制的机制基础以及在改变氧气供应时对其进行修改的方式甚至更不为人所知，因为增加供应与减少需求之间的平衡是精心策划的。利用物种差异（个体发生），发育变化（个体发生）和遗传操作作为工具，我和我的学生希望确定代谢供需匹配机制的方式，以满足生活在不同环境中的脊椎动物的需求。