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(2+) 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(2+) obviously inhibits the current of the hERG K(+) channel, and delays the "activation" and "deactivation" of the hERG K(+) channel, indicating that Pb(2+) evidently decreases the function of the K(+) channel in the cell. The effect is increased with increasing the concentration of Pb(2+). When the concentration of Pb(2+) 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 Pb(2+) 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(2+), it would affect the treatment and prognosis of Pb(2+) intoxication.
Zhou
Jiemin
J
The First School of Clinical Medicine, Nanjing Medical University, Nanjing 210097, People's Republic of China.
Hu
Gang
G
D002460:Cell Line; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007854:Lead / Q000633:toxicity*; D056004:Molecular Dynamics Simulation
D051638:Ether-A-Go-Go Potassium Channels; D007854:Lead