High-Throughput Screening Of Ion Channel Variants Using Automated Patch Clamp Recordings In Assay Ready Cells

Ion channels are crucial for regulating ion flow in and out of cells, and their pathogenic variants are linked to conditions like epilepsy. This study introduces a high-throughput method for assessing KCNQ2 ion channel variants, which are associated with various neurodevelopmental disorders and epilepsies. The approach utilizes electroporation to create "Assay Ready Cells" suitable for automated patch clamp recordings, enabling large-scale characterization of ion channel variants. This method was used to characterize 39 previously unstudied epilepsy-associated Q2 variants and their responses to a candidate therapeutic, retigabine.

This technique offers a consistent and efficient way to generate reliable data on hundreds of variants, which is essential for identifying patients who could benefit from new precision medicines.