Cell and Tissue Responses to Electric Shocks Invited Paper

Existing models of myocardial membrane kinetics have not been able to reproduce the experimentally-observed negative bias in the asymmetry of transmembrane potential changes (DeltaV_m) induced by strong electric shocks. The goals of this study are: 1) to demonstrate that this negative bias could be reproduced by the addition, to the membrane model, of electroporation and an outward current, I_a, part of the K⁺ flow through the L-type Ca²⁺-channel, and 2) to determine how such modifications in the membrane model affect shock-induced break excitation in a 2D preparation. We conducted simulations of shocks in bidomain fibers and sheets with membrane dynamics represented by the LRd´2000 model, to which electroporation (LRd+EP model) and the outward current, I_a , activated upon strong shock-induced depolarization (aLRd model) was added. Assuming I_a is a part of K⁺ flow through the L-type Ca²⁺-channel enabled us to reproduce both the experimentally observed rectangularly-shaped positive DeltaV_m and the value of near 2 of the negative-to-positive deltaV_m ratio. In the sheet, I_a not only contributed to the negative bias in DeltaV_m asymmetry at sites polarized by physical and virtual electrodes, but also restricted positive DeltaV_m. Electroporation, in its turn, was responsible for the decrease in cathode-break excitation threshold in the aLRd sheet, as compared to the other two cases, as well as for the occurrence of the excitation after the shock-end rather than during the shock. The incorporation of electroporation and I_a in a membrane model ensures match between simulation results and experimental data. The use of the aLRd model results in a lower threshold for shock-induced break excitation