Characterization of hiPSC-derived neurological disease models using automated patch clamp (Qube and QPatch)
Human induced pluripotent stem cells (hiPSCs) can be differentiated into multiple cell types, including neurons and cardiomyocytes, which can be used as human disease models for in vitro drug development. Ion channels represent highly attractive therapeutic targets in the nervous and the cardiovascular system2, rendering electrophysiological studies of hiPSCs important for their usage in drug discovery. However, such studies have traditionally been limited by the labour-intensive and low-throughput nature of patch clamp electrophysiology.
Here we present the electrophysiological characterization of hiPSC-derived motor neurons using our automated patch clamp (APC) platforms, Qube 384 and QPatch. Our observations include channel expression versus time in culture, the pharmacological dissection of endogenous ion channels (e.g. NaV and KV), identification of ligand-gated receptors and recordings of action potentials.
Utilizing the high-throughput nature of our systems we tested in parallel two disease models, using hiPSC neurons derived from Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS) patients, together with control cells from healthy subjects and isogenic control cells. The results indicate an over-expression of Na+ channels in both cell lines, which could be rescued by a point mutation in the superoxide dismutase (SOD1) gene in the isogenic ALS cell line.