Effects of the Small Conductance Calcium-Activated Potassium Current (ISK) in Human Sinoatrial Node

The description of the underlying phenomena that modulate the heart rate is crucial to better understand arrhythmias. Computational models are powerful tools to investigate the contribution of ion currents to the changes of membrane potential. Among them, the calciumactivated small conductance K+ current (ISK) is able to modulate the action potential (AP) duration and rate. The aim of this work was to assess how the inclusion of ISK affected the AP and calcium transient features of the human sinoatrial node model we recently developed. The formulation of ISK was adopted according to Kennedy et al. and a sensitivity analysis on gSK (gSK = 0, 4, 10, 41.70 µS/µF) was carried out. The main effects of ISK were an overall reduction of cycle length (CL) (from 814 ms in CTRL to 764, 668 and 439 ms for gSK = 4, 10, 41.70 µS/µF, respectively) due to a decrease of the AP duration at 90% of repolarization (APD90) (from 161 ms in CTRL to 155.0, 143.0 and 96.0 ms) and an increase of the diastolic depolarization rate in the first 100 ms (DDR100) (from 48.1 mV/s to 52.9, 60.6 and 87.2 mV/s). The reduction of CL due to the shortening of APD90 was predictable, since ISK is an outward current. The increase of DDR100 led to the shortening of the DD phase. This was an unexpected effect of the inclusion of ISK: the latter reduced the contribution of the rapid delayed rectifier K+ current (IKr), which compensated and even overcame the outward contribution of ISK.