Archiv - Januar 2009

Functional and molecular analysis of GABA receptors in human midbrain-derived neural progenitor cells.

Florian Wegner*,†, Robert Kraft‡, Kathy Busse§, Wolfgang Härtig¶, Grit Schaarschmidt*, Sigrid C. Schwarz*, Johannes Schwarz*,†,1 and Wulf Hevers‡,1
*Department of Neurology, University of Leipzig, Leipzig, Germany
†Translational Centre of Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany
‡Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany
§Department of Molecular Biochemistry, Institute of Biochemistry, University of Leipzig, Leipzig, Germany
¶Department of Neurophysiology, Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany Division of Endocrinology and Diabetology, Department of Internal Medicine, University of Leipzig, Philipp-Rosenthal-Strasse 27, D-04103 Leipzig, Germany

J Neurochem. 2008 Nov;107(4):1056-69.


GABAA receptor function is involved in regulating proliferation, migration, and differentiation of rodent neural progenitor cells (NPCs). However, little is known about the molecular composition and functional relevance of GABAA receptors in human neural progenitors. Here, we investigated human fetal midbrain-derived NPCs in respect to their GABAA receptor function and subunit expression using electrophysiology, calcium imaging, and quantitative real-time PCR. Whole-cell recordings of ligand- and voltage-gated ion channels demonstrate the ability of NPCs to generate action potentials and to express functional GABAA receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular characterizations indicate a predominance of GABAA receptor heteromers containing subunits α2, β1, and/or β3, and γ. Intracellular Ca2+ measurements and the expression profile of the Na+–K+–Cl− co-transporter 1 and the K+–Cl− co-transporter 2 in differentiated NPCs suggest that GABA evokes depolarizations mediated by GABAA receptors. These data indicate that NPCs derived from human fetal midbrain tissue acquire essential GABAA receptor properties during neuronal maturation in vitro.

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