Sertraline Blocks Human HERG K+ Channels
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In this study, we used whole-cell patch clamp techniques to investigate the effect of sertraline, a selective serotonin reuptake inhibitor, on human ether-a-go-go-related gene (HERG) channels expressed in human embryonic kidney cells. Sertraline inhibited HERG channels in a concentration-dependent manner, with an IC50 value of 0.83 μM and a Hill coefficient of 1.58, as analyzed based on peak tail current. These effects could be reversed after the drug was washed away. Sertraline inhibited HERG channels in a voltage-dependent manner. The inhibition was dramatically enhanced across the channel-opening voltage range. However, in the voltage range where the channel was fully activated, the degree of inhibition did not change, indicating that it was not affected by voltage changes. The fractional electrical distance was calculated to be 0.025, and HERG channel blockade was independent of use. The blocking characteristics depended on the channel being in the open and inactivated states, rather than the closed state. These results suggest that sertraline binds to HERG channels in both the open and inactivated states, thereby blocking them.
Abstract
In this study, we used whole-cell patch clamp techniques to investigate the effect of sertraline, a selective serotonin reuptake inhibitor, on human ether-a-go-go-related gene (HERG) channels expressed in human embryonic kidney cells. Sertraline inhibited HERG channels in a concentration-dependent manner, with an IC50 value of 0.83 μM and a Hill coefficient of 1.58, as analyzed based on peak tail current. These effects could be reversed after the drug was washed away. Sertraline inhibited HERG channels in a voltage-dependent manner. The inhibition was dramatically enhanced across the channel-opening voltage range. However, in the voltage range where the channel was fully activated, the degree of inhibition did not change, indicating that it was not affected by voltage changes. The fractional electrical distance was calculated to be 0.025, and HERG channel blockade was independent of use. The blocking characteristics depended on the channel being in the open and inactivated states, rather than the closed state. These results suggest that sertraline binds to HERG channels in both the open and inactivated states, thereby blocking them.