Reactive oxygen species impair the excitation-contraction coupling of papillary muscles after acute exposure to a high copper concentration.

Copper is an essential metal for homeostasis and the functioning of living organisms. We investigated the effects of a high copper concentration on the myocardial mechanics, investigating the reactive oxygen species (ROS) mediated effects. The developed force of papillary muscles was reduced after acute exposure to a high copper concentration and was prevented by co-incubation with tempol, DMSO and catalase. The reuptake of calcium by the sarcoplasmic reticulum was reduced by copper and restored by tempol. The contractile response to Ca was reduced and reversed by antioxidants. The response to the β-adrenergic agonist decreased after exposure to copper and was restored by tempol and catalase. In addition, the in situ detection showed increased O- and OH. Contractions dependent on the sarcolemmal Ca influx were impaired by copper and restored by antioxidants. Myosin-ATPase activity decreased significantly after copper exposure. In conclusion, a high copper concentration can acutely impair myocardial excitation-contraction coupling, reduce the capacity to generate force, reduce the Ca inflow and its reuptake, and reduce myosin-ATPase activity, and these effects are mediated by the local production of O-, OH and HO. These toxicity effects of copper overload suggest that copper is a risk factor for cardiovascular disease.