Blocking L-Type Calcium Current Reduces Vulnerability to Re-Entry in Human iPSC-Derived Cardiomyocytes Tissue

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have proven to be crucial in pharmacological assessment. Nevertheless, their response to drugs when coupled forming a tissue is not fully understood. Thus, the aim of this study was to determine whether blocking L-type Ca+2 current (ICaL) in a hiPSC- CMs tissue could be considered as a potential antiarrhythmic procedure.To analyze the effects of ICaL block, the maximum conductance of ICaL (gCaL) was decreased (block conditions) and compared to control. In both situations, control and block, the tissue was stimulated following a cross-field protocol to generate re-entries. A phase analysis was performed and specific parameters, such as re-entry frequency (freentry), excitation wavelength, vulnerable window (VW), and cellular excitability, were evaluated.Induced re-entries, where ICaL was reduced by 70% showed a 6.9% and a 47.83% decrease in freentry and in the width of the VW, respectively. Our results suggest that blocking calcium channels could be considered as an antiarrhythmic strategy in a hiPSC-CMs tissue.