Integrated cardiorespiratory physiology

综合心肺生理学

• 批准号: RGPIN-2015-05059
• 负责人: Farrell, Anthony
• 金额: $ 6.56万
• 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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613331
• 关键词: Integrated; cardiorespiratory; physiology

I study the heart, an organ that powers the cardiorespiratory system. I aim to discover mechanisms and unifying concepts that explain how different cardiac designs assist animals to live at a high environmental temperature or with low (or no) O2. One theme of my research program will provide new insights into specialized ion channels in cardiac cell membranes that are key to allowing an animal’s heartbeat to be automatic and rhythmic. We will investigate how the heartbeat is physiologically initiated and controlled when these channels open for ion movements. Also, a phylogenetic tree of the molecular structure of these ion channels will be created for hagfish (representatives of earliest chordates), cartilaginous fishes (at the base of the vertebrate lineage) and lungfish (at the base of the tetrapod lineage). A second theme builds on our physiological studies of rainbow trout populations that, through natural selection or hatchery practices, live at unusually high temperatures for this species. We will explore molecular mechanisms (changes to DNA and in RNA expression) that allow regular heartbeats at what would be normally a supra-optimal temperature for the species. By extension, we will see if Antarctic and Arctic fishes can express a new cardiac design and maintain physiological function after being warmed to temperatures realistic for global climate change. Hemoglobin-free icefish will be studied in Antarctica (an expedition funded by the USA’s National Science Foundation), while Arctic cod will be shipped to and acclimated in UBC’s new aquatic facility. Lastly, to enlighten how the first vertebrates may have developed a more secure O2 supply for their heart, we will complete our comprehensive phylogenetic and physiological exploration of the coronary circulation in cartilaginous fishes. Because all animals do not possess a coronary circulation and by studying representatives of basal vertebrates in which the coronary circulation first appeared, we will identify factors that likely drove the evolution of an O2 delivery system that better secures heart function when it must continue beating in extreme conditions. Thus, my research program will generate basic morphological, physiological and molecular information that help explain how cardiac structure and function ensure an adequate O2 supply for an animal. This information is of great significance to Canadians given the increased warming of our Arctic Ocean and the eutrophication our freshwater.

我研究心脏，一个为心肺系统提供动力的器官。我的目标是发现机制和统一的概念，解释不同的心脏设计如何帮助动物在高环境温度或低（或无）氧环境下生活。我的研究项目的一个主题将为心脏细胞膜上的特殊离子通道提供新的见解，这是使动物的心跳自动和有节奏的关键。我们将研究当这些通道为离子运动打开时，心跳是如何在生理上启动和控制的。此外，还将为盲鳗（最早脊索动物的代表）、软骨鱼（脊椎动物谱系的基础）和肺鱼（四足动物谱系的基础）创建这些离子通道分子结构的系统发育树。第二个主题建立在我们对虹鳟鱼种群的生理研究上，通过自然选择或孵化场实践，虹鳟鱼种群生活在异常高的温度下。我们将探索分子机制（DNA和RNA表达的变化），使正常的心跳在对物种来说通常是超理想的温度下。由此，我们将看到南极和北极的鱼类在被加热到与全球气候变化相适应的温度后，是否能表现出一种新的心脏设计，并保持生理功能。无血红蛋白的冰鱼将在南极洲进行研究（由美国国家科学基金会资助的一次考察），而北极鳕鱼将被运往UBC的新水生设施并适应。最后，为了揭示第一批脊椎动物是如何为心脏提供更安全的氧气供应的，我们将完成对软骨鱼冠状动脉循环的全面系统发育和生理探索。因为不是所有的动物都有冠状动脉循环，通过研究冠状动脉循环首次出现的基础脊椎动物的代表，我们将确定可能推动氧气输送系统进化的因素，当它必须在极端条件下继续跳动时，它可以更好地保护心脏功能。因此，我的研究项目将产生基本的形态学、生理学和分子信息，帮助解释心脏的结构和功能如何确保动物充足的氧气供应。鉴于北冰洋变暖加剧和淡水富营养化，这一信息对加拿大人来说意义重大。