Regulation of contractility in the teleost heart

NSERC的这一研究项目致力于研究鱼类心脏跳动强度的调节机制。虽然我们的主要兴趣是鲑科鱼类，包括虹鱼、红三文鱼和钢头鱼，但其他在较温暖水域中活动的鱼类(例如斑马鱼和罗非鱼)将从进化的角度进行研究。鲑鱼在加拿大具有重要的社会、经济和战略意义。鱼类心脏的功能在生理学上引起了极大的兴趣，因为它们的水生栖息地使它们暴露在水离子浓度(包括钙和钠)、水温和pH的突然和具有挑战性的变化中，这是哺乳动物在陆地环境中没有经历过的。因此，这个研究项目的一个主要目标是了解环境差异是如何决定这些生物心脏的分子设计的。另一个主要目标是了解环境变化(如温度和pH)如何在分子和细胞水平上显著影响硬骨鱼心脏的基本调节机制，从而影响心脏的收缩能力。心脏的收缩能力有很大的变化，但在节拍的基础上受到输送到收缩元件的钙(Ca)的量和/或收缩元件对钙的敏感性的调节。因此，这项研究计划将重点放在组成鱼心的细胞中特定蛋白质的结构和功能，这些蛋白质调节钙的输送和清除，以及对这些信号的收缩反应。我们将使用生物信息学、分子生物学、共聚焦显微镜、生物物理学和生理学的技术。

This NSERC program of research addresses the mechanisms by which the strength of the heart beat is regulated in fish. Although our primary interest is the salmonids which include rainbow trout, sockeye salmon and steelhead, other fish which function in warmer waters (e.g. zebrafish and tilapia) will be studied for an evolutionary perspective. The salmonids are of great importance socially, economically and strategically in Canada. How hearts from fish function is of great interest physiologically because their aquatic habitat exposes them to sudden and challenging changes in water ion concentrations (including Ca and Na), water temperature and pH that are not experienced by mammals in their terrestrial environments. Thus a major objective in this program of research is to understand how the environmental differences have dictated the molecular design of the hearts of these organisms. Another major objective is to understand how environmental changes (e.g. temperature and pH) acutely impact the basic regulatory mechanisms in the teleost heart on a molecular and cellular level, thereby impacting cardiac contractility. Cardiac contractility is quite variable but is regulated on a beat-to-beat basis by the amount of calcium (Ca) delivered to the contractile element and/or the sensitivity of the contractile element to Ca. Thus this program of research will focus on the structure and function of specific proteins in the cells that make up fish heart that regulate calcium delivery and removal and the contractile response to these signals. We will use techniques from bioinformatics, molecular biology, confocal microscopy, biophysics and physiology.