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

Abstract

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.

Attention-deficit/hyperactivity disorder associated with KChIP1 rs1541665 in Kv channels accessory proteins

“…Luo M et al discovered the epigenetic mechanism bridging lead and ADHDin the histone modification level [ 70 ], and early life-lead exposure altered gene expression patterns and global methylation profiles, suggesting that lead caused neurotoxicity by gene interactions [ 71 , 72 ]. Besides, lead can coordinate with the oxygen/sulfur atoms in the K channel protein, leading to the decrease in the function of the Kchannel [ 73 ]. Thus, we speculated that the lead and Kv channels may work together in ADHD.…”

Effect of 3 Weeks of Balneotherapy on Immunological Parameters, Trace Metal Elements and Mood States in Pilots

“…Cd and Pb are widely distributed heavy metals which can induce a broad range of physiological, biochemical, and behavioral dysfunctions in laboratory animals and humans [20][21][22] . This includes age-specific variations in absorption, retention, and tissue distribution of Pb.…”