Metal-induced inhibition of Na+/K+-ATPase and SERCA in the rainbow trout (Oncorhynchus mykiss) heart: implications for cardiac ion regulation

Metal ions are known to inhibit sarcolemmal ion currents and induce cardiac arrhythmias in fish, but their actions are not fully explained by ion channel blockade. To further clarify the effects of di- and trivalent cations on fish heart function, we examined the impact of eight metals on the activities of Na ⁺ /K ⁺ -ATPase and Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA) in rainbow trout ( Oncorhynchus mykiss ) ventricle. Unfractionated ventricular homogenates were exposed in vitro to eight metals (Al ³⁺ , Mn ²⁺ , Fe ²⁺ , Co ²⁺ , Ni ²⁺ , Cu ²⁺ , Zn ²⁺ or Hg ²⁺ ) at concentrations of 0.1–30 µM. Na ⁺ /K ⁺ -ATPase activity was strongly inhibited by Hg ²⁺ and Cu ²⁺ in a concentration-dependent manner, with IC50 values of 1.4 ± 0.13 µM and 3.2 ± 1.0 µM, respectively, and Na ⁺ /K ⁺ -was less sensitive to Zn ²⁺ (IC50 10.6 ± 2.9 µM). Other metals had little or no effect. SERCA activity was inhibited only by Hg ²⁺ (IC50 value of 2.6 ± 0.7 µM). The inhibition of Na ⁺ /K ⁺ -ATPase and SERCA by Hg ²⁺ occurred at concentrations comparable to those previously associated with cardiac arrhythmias in rainbow trout. These findings suggest that the arrhythmogenic effects of Hg ²⁺ (and possible other metals) arise not only from voltage-gated channel blockade but also from inhibition of active ion transport across the sarcolemma and reduced Ca ²⁺ uptake by the sarcoplasmic reticulum. We propose that the inhibition of Na ⁺ /K ⁺ -ATPase by Hg ²⁺ and Cu ²⁺ , and of SERCA by Hg ²⁺ , causes cytosolic Ca ²⁺ overload, which may trigger early and delayed afterdepolarizations and ultimately lead to arrhythmic activity in the fish heart.