Mechanisms of cardiotoxicty-related mortality in fish

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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.