differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits神经祖细胞分化人类midbrain-derived表达兴奋strychnine-sensitive包含α2β亚基甘氨酸受体.pdfVIP

Differentiated Human Midbrain-Derived Neural Progenitor Cells Express Excitatory Strychnine-Sensitive Glycine Receptors Containing a2b Subunits 1 2 3 ¨ 4 ¨ 5 5 Florian Wegner *, Robert Kraft , Kathy Busse , Wolfgang Hartig , Jorg Ahrens , Andreas Leffler , Reinhard Dengler1, Johannes Schwarz3 1 Department of Neurology, Hannover Medical School, Hannover, Germany, 2 Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany, 3 Department of Neurology, University of Leipzig, Leipzig, Germany, 4 Department of Neurophysiology, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany, 5 Department of Anaesthesiology and Intensive Care, Hannover Medical School, Hannover, Germany Abstract Background: Human fetal midbrain-derived neural progenitor cells (NPCs) may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson’s disease. While glutamate and GABAA receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. Methodology/Principal Findings: Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing a2b subunits. Intracellular calcium measurements of d