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An in Silico Investigation Into The Role of SK Channels in Failing Ventricular Myocytes

Abstract:

SK channels are small conductance (10 pS) calcium-activated potassium channels. Although they have been suggested not to play a relevant role in healthy ventricles, SK channel upregulation has been reported in failing ventricles, with potential implications for arrhythmogenesis. In this work, we aimed at uncovering the contribution of SK channels to ventricular repolarization in failing myocytes. To that end, we extended an in silico electrophysiological model of human ventricular failing myocytes by introducing the equations representing SK channel activity. To determine the value of the maximal SK current conductance, GSK' we simulated action potentials (APs) at different pacing frequencies and we fitted the changes in AP duration induced by SK channel inhibitions to available experimental data recorded under pharmacological inter-ventions. The SK block-induced effects in our simulations were consistent with experimental evidence. Early after-depolarizations were observed at pacing frequencies below 0.7 Hz only when SK channels were blocked. In conclusion, our presented model of human ventricular failing myocytes integrating an SK channel formulation can allow dissecting the contribution of SK channels to ventricular repolarization and may help in understanding their role in arrhythmogenesis.