Electrophysiological characterization of iPSC-derived excitatory neurons, including a comparison to genetically modified Frontotemporal Dementia neuron model, using automated patch clamp


Stem Cells in Neuroscience 2024


Stefania Karatsiompani, Scott Schatchtele, Kadla R. Rosholm



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 apparently healthy normal (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 and how they develop over time. We also compare action potential parameters (such as spike frequency, spike threshold and action potential amplitude) in WT and FTD model iPSC-derived excitatory neurons.

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