Mechanisms of cardiotoxicty-related mortality in fish

石油泄漏、工业废物进入流域和农药径流等环境灾难往往与鱼类死亡有关。在这种情况下的死因仍不确定，但可能与快速、不规则的心跳(心悸)有关，心跳减少了心脏泵送的血量，随着时间的推移，这可能会导致器官衰竭和死亡。或者，心脏搏动也可能完全停止。由于心脏收缩是由电事件(心脏动作电位)触发的，动作电位的产生异常可能是导致死亡的不规则心跳的基础，而动作电位的缺乏可能导致心跳停止。之前使用胚胎或基因操纵的鱼类心脏细胞的研究表明，环境毒素可能会导致心脏跳动不规律和停止跳动。然而，这些影响发生的确切机制还没有确定，也没有像野外发生的那样，在成鱼心脏细胞急性暴露于环境毒素后证明这些影响。我们建议系统地研究选定的环境毒素(二恶英、多溴二苯醚和原油成分，如多环芳烃)对幼年和成年斑马鱼心脏细胞电活动的影响，以表征这些毒素对动作电位特征和产生动作电位的单个离子电流特性的影响。识别毒素引起的心脏毒性效应的离子机制可能会导致新的策略来保护鱼类免受环境毒素的影响，可能是通过对鱼类进行基因工程，使它们携带通常以毒素为靶标的离子电流的毒素免疫变体。这种战略可以减少环境灾难对渔业的经济影响，并保护濒危或其他重要鱼种。

Environmental catastrophes such as oil spills, introduction of industrial waste into watersheds and pesticide run-offs often are associated with fish kills. The cause of death under these circumstances is still uncertain, but it may relate to a rapid, irregular heartbeat (palpitations), which reduces the amount of blood pumped by the heart, which over time can cause organ failure and death. Alternatively, complete cessation of heart pumping may occur. Because contraction of the heart is triggered by an electrical event, the cardiac action potential, abnormalities in the generation of action potentials may underlie the irregular heartbeats that cause death and an absence of action potentials may cause cessation of beating. Previous studies using embryonic or genetically manipulated fish heart cells have suggested that environmental toxins may cause both irregular beating and the cessation of beating. However, the exact mechanisms by which these effects occur have not been defined, nor have these effects been demonstrated following acute exposure of adult fish heart cells to environment toxins, as would occur in the wild. We propose a systematic study of the effects of selected environmental toxins (dioxins, polybrominated diphenyl ethers and crude oil constituents such as polycyclic aromatic hydrocarbons) on the electrical activity of juvenile and adult zebrafish heart cells to characterize the effects of these toxins on action potential characteristics and on the properties of the individual ionic currents that underlie the generation of action potentials. Identification of the ionic mechanisms for toxin-induced cardiotoxic effects could lead to new strategies to protect fish from environment toxins, perhaps by genetically engineering fish so that they carry a toxin-immune variant of the ionic current normally targeted by the toxin. Such a strategy could reduce the economic impact of environmental catastrophes on the fishing industry and offer protection of endangered or otherwise important species of fish.