Electrophysiological characterization of genetically modified iPSC neurons as a frontotemporal dementia model using Automated Patch Clamp – differences in ion channel and action potential properties

Induced pluripotent stem cells (iPSCs) show great potential for the generation and characterization of neuronal subtypes as well as the investigation of neurological disease models. However, in practice the intercellular variability in a population of iPSC-derived neurons in combination with the low-throughput nature of manual electrophysiological experiments, have made such studies challenging.

Here, we use automated patch clamp (APC) for high-throughput characterization and comparison of commercially available healthy (WT) and frontotemporal dementia (FTD; genetically engineered granulin R493X heterozygous knockout)
iPSC-derived excitatory neurons. The results include an optimization of the cell suspension for APC and an analysis of voltage-gated (KV and NaV) and ligand-gated (AMPA) ion channel currents. We also analyze action potential parameters (such as spike frequency, spike threshold and action potential amplitude) in WT and FTD model iPSC-derived excitatory neurons. We see a clear correlation between the functionality of NaV channels and the ability to fire action potentials, with the FTD neurons showing more immature properties.