Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus...

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 °C, and APs were measured at the acclimated temperature and elevated temperature (+18 °C). Cd²⁺ (10, 20, and 100 µM) 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 °C and +18 °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 °C) slightly increases Cd²⁺ toxicity in trout ventricular myocytes. Environ Toxicol Chem 2021;40:2874-2885. © 2021 SETAC.