Development, Implementation and Testing of a Multicellular Dynamic Action Potential Clamp Simulator for Drug Cardiac Safety Assessment

Abstract

As drugs can be multichannel blockers it is important to assess their cardiac safety taking into account multiple currents. In silico action potential (AP) models have been proposed for being able to integrate drugs effect on ionic currents and generate the resulting AP. However, a mathematical description of drug effects is required, which could be inaccurate. Dynamic Clamp has been proposed for drug cardiac safety assessment. In the dynamic action potential clamp (dAPC) configuration it creates an hybrid model connecting a real cell with a computer simulation. This way, drugs could be administrated directly to real cells, and effects on currents can be taken into account when generating the AP. Here we design and simulate a parallel multichannel dAPC system. The system includes the real cells overexpressing the currents of interest, the voltage clamp acquisition system, and the AP in silico model.