Effect of Lead Ion on the Function of the Human Ether-À-Go-Go-Related Gene K Channel.

Lead (Pb) is a trace metal element in the human body. In order to understand the hazard mechanism of the elevated blood lead level on the human body, the effect of Pb on the human ether-à-go-go-related gene (hERG) K channel in the HEK 293 cell was investigated for the first time using whole-cell patch clamp technique, molecular dynamics simulation, and quantum chemistry calculation methods. We found that Pb obviously inhibits the current of the hERG K channel, and delays the 'activation' and 'deactivation' of the hERG K channel, indicating that Pb evidently decreases the function of the K channel in the cell. The effect is increased with increasing the concentration of Pb. When the concentration of Pb is 400 μg L, the function of the K channel is entirely lost. The results from the molecular dynamics simulation and quantum chemistry calculation indicated that Pb can coordinate with the oxygen/sulfur atoms in the K channel protein, leading to the decrease in the function of the K channel. According to the experimental results, we suggested that once the K channel in the human body was irreversibly inactivated by Pb, it would affect the treatment and prognosis of Pb intoxication. [ABSTRACT FROM AUTHOR]