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 Pb2+ 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 Pb2+ obviously inhibits the current of the hERG K+ channel, and delays the “activation” and “deactivation” of the hERG K+ channel, indicating that Pb2+ evidently decreases the function of the K+ channel in the cell. The effect is increased with increasing the concentration of Pb2+. When the concentration of Pb2+ is 400 μg L−1, the function of the K+ channel is entirely lost. The results from the molecular dynamics simulation and quantum chemistry calculation indicated that Pb2+ 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 Pb2+, it would affect the treatment and prognosis of Pb2+ intoxication.