
New Application Report explains how to optimize cardiac electrophysiology recordings with perforated automated patch clamp on Qube 384
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer the potential to revolutionize cardiac disease modeling and drug screening. However, capturing physiologically relevant action potentials (APs) has been challenging, particularly with traditional whole-cell (WC) patch clamp methods. WC recordings disrupt the cellular environment, often resulting in shorter AP durations due to the âwash-outâ of cytoplasmic components.
Using the perforated patch clamp method it is possible to preserve cellular integrity while having electrical access. Unlike WC, the perforated approach uses agents like nystatin to form small pores in the cell membrane, allowing the passage of ions while maintaining essential cytoplasmic components. Applying this method, we demonstrated significant improvements in AP recordings on Sophionâs Qube 384 platform, with success rates of up to 40%.
Key advantages? Larger CaÂČâș currents and prolonged AP durations, which provide a more accurate reflection of cardiomyocyte physiology. Indeed, cells in perforated patch configuration exhibit action potential duration at 30% repolarization (APD30), approximately 60% longer than WC cells. This extended duration highlights better cellular CaÂČâș handling and a more stable membrane environment, making perforated patch clamp recordings an invaluable tool for cardiac drug discovery and disease modeling.
By offering a clearer window into ion channel behavior and AP morphology, the perforated patch technique on Qube 384 is paving the way for more precise and reliable cardiac electrophysiology experiments, whilst providing a high throughput assay essential for cardiovascular disease studies, safety pharmacology, drug discovery and development.