Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are an interesting source of cells for safety pharmacology, but there are caveats that have to be taken into account. A typical property of hPSC-CM is automaticity, the cardiomyocytes beat spontaneously, resembling cells in the sinoatrial node of the heart. The spontaneous beating is due to lack of IK1 ion channels, which normally assure a stable resting membrane potential in cardiomyocytes. Work by our group has demonstrated that the depolarized state of hPSC-CM limits their usefulness in assays aimed at detecting proarrhythmic properties of drugs (Jonsson et al., 2012, PMID: 22353256).
Dynamic clamping can provide virtual, simulated IK1 channels to a real biological hPSC-CM in a patch clamping experiment. Key benefits of this approach include full control of the added IK1 conductance to each cardiomyocyte, it can be applied to any hPSC-CM source and it can be coupled to automated patch clamping machines. In this webinar I will discuss our work on using the dynamic clamping technique with a Patchliner.