Regulation of myocardial contractility in salmonids

这些研究将探讨鲑科鱼类调节心脏功能的机制。鲑科鱼类包括鲑鱼和鳟鱼，它们在加拿大占据着重要的生物和商业生态位。然而，不断变化的环境条件对这些物种构成了真正的威胁。两个重要的条件是全球变暖和海水酸化。这些动物受到威胁，部分原因是这些环境变化可能损害心血管功能，因此是致命的。这些鱼对我们对心脏收缩的理解提出了一个有趣的挑战，因为它们的心肌在一系列温度下运行，对人类来说是心脏瘫痪的。从生理实验中，我们已经预测了几种对心脏收缩性调节至关重要的蛋白质已经适应了在不同条件下保持收缩性。因此，pH和温度对鲑鱼心脏基本调节机制的影响将被详细研究。心脏收缩的强度在搏动的基础上由传递给收缩元件（CE）的钙（Ca）的量和/或CE对Ca的反应来调节。Na-Ca交换器（NCX）是钙从心肌细胞外排的主要机制，也是钙内流的可能调节剂。肌钙蛋白C （TnC）是细胞内钙升高时启动收缩的关键蛋白。因此，本项目将重点研究鲑科鱼心脏中NCX和TnC的分子特征，利用分子生物学技术来设计新分子。来自鱼心脏的单细胞（心肌细胞）也将被研究，以将分子生物学实验置于生理环境中，包括pH和温度的变化。这些实验的重要性包括这些数据：a)对于详细了解鱼心脏的生理学至关重要，b)应该为这些蛋白质在哺乳动物中的结构/功能关系提供有趣的见解，c)可能有助于提高在不断变化的水条件下的生存能力，d)应该深入了解进化压力，因为硬骨鱼与人类的进化距离约为3.5亿年。

These studies will address the mechanisms by which cardiac function is regulated in the salmonids, a group that includes salmon and trout, which occupy an important biological and commercial niche in Canada. However, changing environmental conditions represent a real threat to these species. Two conditions of significance are global warming and the acidification of our waters. These animals are threatened, in part, because of the potential of these environmental changes to compromise cardiovascular function and hence are lethal. These fish pose an interesting challenge to our understanding of cardiac contraction as their myocardium functions over a range of temperatures that are cardioplegic to humans. From physiological experiments, we have predicted that several proteins critical to the regulation of cardiac contractility have adapted to allow contractility to be maintained under diverse conditions. Thus the effects of pH and temperature on the basic regulatory mechanisms in the salmonid heart will be studied in detail. The strength of cardiac contraction is regulated on a beat-to-beat basis by the amount of calcium (Ca) delivered to the contractile element (CE) and/or the response of the CE to Ca. The Na-Ca exchanger (NCX) is the primary mechanism of Ca efflux from the myocyte and is also a possible regulator of Ca influx. Troponin C (TnC) is the critical protein that initiates contraction in response to elevated intracellular Ca. Thus this project will focus on the molecular characterization of NCX and TnC in the salmonid heart using molecular biological techniques to engineer new molecules. Single cells from the fish heart (cardiomyocytes) will also be studied to place the molecular biology experiments into a physiological context including changes in pH and temperature. The importance of these experiments includes the fact that these data: a) are critical for a detailed understanding of the physiology of the fish heart, b) should provide interesting insight into the structure/function relationship of these proteins in mammals, c) may be useful in to improve survivability in changing water conditions, and d) should give insight into the evolutionary pressure, since the teleosts are separated from humans by ~350 million years of evolution.