Toxic effects of environmental rare earth elements on delayed outward potassium channels and their mechanisms from a...

The wide applications cause a large amount of rare earth elements (REEs) to be released into the environment, and ultimately into the human body through food chain. Toxic effects of REEs on humans have been extensively studied, but their toxic effects and binding targets in cells are not understood. Delayed outward potassium channels (K⁺ channels) are good targets for exogenous substances or clinical drugs. To evaluate cellular toxicities of REEs and clarify toxic mechanisms, the toxicities of REEs on the K⁺ channel and their structural basis were investigated. The results showed that delayed outward potassium channels on the plasma membrane are the targets of REEs acting on living organisms, and the changes in the thermodynamic and kinetic characteristics of the K⁺ channel are the reasons of diseases induced by REEs. Two types of REEs, a light REE La³⁺ and a heavy REE Tb³⁺, displayed different intensity of toxicities on the K⁺ channel, in which the toxicity of Tb³⁺ was stronger than that of La³⁺. More interestingly, in comparison with that of heavy metal Cd²⁺, the cytotoxicities of the light and heavy REEs showed discriminative differences, and the cytotoxicity of Tb³⁺ was higher than that of Cd²⁺, while the cytotoxicity of La³⁺ was lower than that of Cd²⁺. These different cytotoxicities of La³⁺, Tb³⁺ and Cd²⁺ on human resulted from the varying binding abilities of the metals to this channel protein.