SK channels are small conductance (∼10 pS) calcium-activated potassium channels that do not play a relevant role in normal ventricular electrophysiology. However, studies suggest that blocking SK channels may have significant ventricular effects in pathological conditions, with potential implications for arrhythmogenesis. In particular, the pathophysiological role of ventricular SK channels in heart failure (HF) is poorly understood.
In a previous in silico study, SK channel block was found to increase transmural dispersion of repolarization (TDR) in a 1D ventricular fiber, which can correlate with arrhythmia risk in patients with heart failure (HF). The current study investigates the sensitivity of the model's response to small variations in the SK channel conductance (G_SK) of the epicardial and endocardial layers, to assess whether the proarrhythmic effects of the SK channel block can be considered a consistent prediction of the model.
To this end, five G_SK values were selected within a range previously identified from experimental studies. A total of 25 different scenarios were simulated, combining G_SK values in the epicardial and endocardial layers of a 1.70 cm-long ventricular fiber. In each case, the repolarization time (RT) and TDR were computed, and QT intervals were measured from pseudo-ECGs. Finally, variations in TDR and QT interval caused by 100% SK channel block were calculated.
As a result, SK channel block increased TDR and prolonged the QT interval in most scenarios (19 of 25), except when G_SK was substantially higher in the epicardial layer than in the endocardial layer. As these effects predispose to ventricular arrhythmias, our results support the notion that pharmacological SK channel inhibition may be proarrhythmic in heart failure.