Regulation of myocardial contractility in salmonids

点击翻译按钮获取中文摘要

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.