Key result
Simulations of hERG gene mutations demonstrated a positive correlation between the APD90 length and the percentage of current reduction, and between APD90 and RR interval lengths.
Computational modeling demonstrates that specific hERG mutations associated with protein trafficking problems prolong action potential duration, correlating with the degree of rapid delayed rectifier current reduction.
May suggest arrhythmia risk in hERG mutation carriers; leaves open need for clinical validation of these simulations.
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.
No takes yet. Share an insight, caveat, or question.
Glinka et al. (2013) studied hERG gene mutations and cardiomyocyte repolarization impairment. hERG gene mutations (F805C, G601S, D456Y, I31S, R823W, F640V, and A561V) vs. Wild type was evaluated on Action potential duration (APD90). Simulations of hERG gene mutations demonstrated a positive correlation between the APD90 length and the percentage of current reduction, and between APD90 and RR interval lengths.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: