A modular method for high-throughput measurement of ion channel currents in cardiac myocytes

The patch-clamp technique offers unparalleled insight into the electrical and biophysical behavior of excitable cells. However, it is a slow and low-throughput method that typically requires cells to be measured one by one. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are regularly subjected to this technique to unravel the molecular mechanisms of cardiac diseases. Their use in direct patient treatment and successful drug development has been limited due to the lack of applicable high-throughput patch-clamp methods suited to successful hiPSC-CM measurement. Here we present a protocol employing a patch-clamp robot that addresses these limitations by using planar patch-clamp technology. We outline how to collect and handle hiPSC-CM for these experiments, along with optimized patch-clamp protocols for direct functional measurement of major cardiac ion channels including K