Abstract

GlyR and GABAAR Targeted High-throughput Screening and Toxicity Testing Using Human Pluripotent Stem Cells

Katharina Kuenzel, Researcher, FAU Erlangen-Nuremberg, Institute of Medical Biotechnology

Pluripotent stem cells like the human embryonal carcinoma cell line NT2 provide an enormous potential for drug discovery and toxicity testing. NT2 cells differentiate upon exposure to retinoic acid into cells with properties of neurons of the central nervous system and have been shown to express ion channels including glycine receptors (GlyRs) and gamma-aminobutyric acid receptors (GABAARs) which are both increasingly considered as attractive drug targets for therapeutic intervention. By stable transfection of NT2 cells with YFP-I152L, a halide-sensitive YFP (yellow fluorescent protein) variant, we created a cell line for studying the pharmacological properties of GlyRs and GABAARs in native neurons. In concentration-response experiments with the receptor agonist glycine and GABA as well as with receptor-specific drugs we demonstrated the applicability of the established NT2-YFP-I152L cell line for in vitro-based drug and toxicity testing in high-throughput screening format.

Co-authors of this work:  Dr. Daniel Gilbert and Prof. Oliver Friedrich.