Combining in-silico cardiac action potentials with HERG currents expressed in HEK cells using dynamic clamp in synthetic cell mode

Abstract

We used real-time dynamic clamp to allow heterologously-expressed cloned ion channel currents expressed in cells to be input into an in silico cardiac action potential (AP) model (Synthetic Cell Mode). The effect of dofetilide, a HERG blocker, on AP duration was measured. HERG currents were recorded from a stable cell line (HERG_A:HEK, BPS Bioscience) in whole cell voltage clamp. HERG currents were monitored until stable. In Synthetic Cell Mode, we input the HERG current into an in silico AP model consisting of electronically expressed INa, IK1, IKS, ICa_L and Ito.