An analysis of cardiomyocytes’ electrophysiology in the presence of the hERG gene mutations

Abstract Mutations in the human ether-à-go-go-related gene are linked with cardiomyocyte repolarization impairment, which, in combination with other factors, can lead to life-threatening arrhythmias. The aim of the study was to demonstrate the effect of selected mutations associated with protein trafficking problems on the action potential of the ventricular cell. To perform the simulations, the O’Hara-Rudy dynamic model was used. The modification of membrane permeability to rapid delayed rectifier current was based on data obtained from in vitro studies with the human embryonic kidney (HEK293) cell line transfected with human genes: wild type and one of the seven mutations (F805C, G601S, D456Y, I31S, R823W, F640V, and A561V). Simulations were carried out for each mutation on epicardial, endocardial, and M-cells with RR interval values of 500, 750, 1000, and 1500 ms. A positive correlation between the APD90 length and the percentage of current reduction and between APD90 and RR interval lengths was observed.

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