Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus mykiss) Ventricular Myocytes

摘要

Cadmium (Cd2+) is cardiotoxic to fish, but its effect on the electrical excitability of cardiac myocytes is largely unknown. To this end, we used the whole-cell patch-clamp method to investigate the effects of Cd2+ on ventricular action potentials (APs) and major ion currents in rainbow trout (Oncorhynchus mykiss) ventricular myocytes. Trout were acclimated to +4 degrees C, and APs were measured at the acclimated temperature and elevated temperature (+18 degrees C). Cd2+ (10, 20, and 100 mu M) altered the shape of the ventricular AP in a complex manner. The early plateau fell to less positive membrane voltages, and the total duration of AP prolonged. These effects were obvious at both +4 degrees C and +18 degrees C. The depression of the early plateau is due to the strong Cd2+-induced inhibition of the L-type calcium (Ca2+) current (I-CaL), whereas the prolongation of the AP is an indirect consequence of the I-CaL inhibition: at low voltages of the early plateau, the delayed rectifier potassium (K+) current (I-Kr) remains small, delaying repolarization of AP. Cd2+ reduced the density and slowed the kinetics of the Na+ current (I-Na) but left the inward rectifier K+ current (I-K1) intact. These altered cellular and molecular functions can explain several Cd2+-induced changes in impulse conduction of the fish heart, for example, slowed propagation of the AP in atrial and ventricular myocardia (inhibition of I-Na), delayed relaxation of the ventricle (prolongation of ventricular AP duration), bradycardia, and atrioventricular block (inhibition of I-CaL). These findings indicate that the cardiotoxicity of Cd2+ in fish involves multiple ion currents that are directly and indirectly altered by Cd2+. Through these mechanisms, Cd2+ may trigger cardiac arrhythmias and impair myocardial contraction. Elevated temperature (+18 degrees C) slightly increases Cd2+ toxicity in trout ventricular myocytes. Environ Toxicol Chem 2021;00:1-12. (c) 2021 SETAC