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

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Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus mykiss) Ventricular Myocytes
Environmental Toxicology and Chemistry ( IF 3.6 ) Pub Date : 2021-07-13 , DOI: 10.1002/etc.5161
Jaakko Haverinen ₁ , Ahmed Badr _{1,

2} , Matti Vornanen ₁

Affiliation

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

中文翻译：

镉的心脏毒性涉及虹鳟（Oncorhynchus mykiss）心室肌细胞中多个离子流之间的复杂相互作用

镉 (Cd ²⁺ ) 对鱼类有心脏毒性，但其对心肌细胞电兴奋性的影响在很大程度上是未知的。为此，我们采用全细胞膜片钳法研究了Cd ²⁺对虹鳟（Oncorhynchus mykiss）心室肌细胞心室动作电位（APs）和主要离子电流的影响。鳟鱼被驯化到+4°C，并在驯化温度和升高的温度（+18°C）下测量AP。镉²⁺（10、20 和 100 µM）以复杂的方式改变了心室 AP 的形状。早期平台期下降到膜电压较低，AP 的总持续时间延长。这些影响在 +4 °C 和 +18 °C 时都很明显。早期高原的抑制是由于强烈的 Cd ²⁺诱导的 L 型钙 (Ca ²⁺ ) 电流 (I _CaL ) 的抑制，而 AP 的延长是 I _CaL抑制的间接结果：在早期高原的低电压下，延迟整流钾（K ⁺）电流（I _Kr）仍然很小，延迟了AP的复极化。Cd ²⁺降低了Na ^{+的密度并减慢了动力学}电流 (I _Na ) 但内向整流器 K ⁺电流 (I _K1 ) 完好无损。这些改变的细胞和分子功能可以解释 Cd ²⁺引起的鱼心脉冲传导的几种变化，例如，心房和心室心肌中 AP 的传播减慢（抑制 I _Na），心室延迟舒张（延长心室 AP 持续时间）、心动过缓和房室传导阻滞（抑制_ICaL）。这些发现表明，Cd ²⁺对鱼类的心脏毒性涉及多种离子流，这些离子流直接和间接地被 Cd ²⁺改变。通过这些机制，Cd ²⁺可能引发心律失常并损害心肌收缩。温度升高 (+18 °C) 会略微增加鳟鱼心室肌细胞中的 Cd ²⁺毒性。环境毒物化学2021；40:2874–2885。© 2021 SETAC

更新日期：2021-07-13

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