Wild type and K897T polymorphisms of the hERG gene: modeling the APD in Caucasians

The presented study aims to assess the possibility of simulating changes in cardiac cell electrophysiology due to K897T polymorphism in the Caucasian population. In the first part of the experiment, the parameters of the equations describing channel gating were fitted to the experimental data. Then, the action potentials of midmyocardial cells of 100 individuals were simulated in the in vitro - in vivo extrapolation system - ToxComp. Mean APD90 for the entire simulated population is 352.05 ms (SD = 21.69 ms). Mean APD90 for the 80 individuals with the WT version of the hERG gene and for the 20 K897T homo- and heterozygotes is respectively 349.08 ms (SD = 21.09 ms) and 363.95ms (SD = 20.41 ms). The ToxComp system can be useful in predicting the impact of genetic variability on drug triggered cardiac cell electrophysiology interference.