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Functional and molecular analysis of GABA A receptors in human midbrain‐derived neural progenitor cells
Author(s) -
Wegner Florian,
Kraft Robert,
Busse Kathy,
Härtig Wolfgang,
Schaarschmidt Grit,
Schwarz Sigrid C.,
Schwarz Johannes,
Hevers Wulf
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05688.x
Subject(s) - receptor , gabaa receptor , microbiology and biotechnology , biology , neural stem cell , neuroscience , calcium imaging , progenitor cell , chemistry , biochemistry , calcium , stem cell , organic chemistry
GABA A 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 GABA A receptors in human neural progenitors. Here, we investigated human fetal midbrain‐derived NPCs in respect to their GABA A 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 GABA A receptors after differentiation for 3 weeks in vitro . Pharmacological and molecular characterizations indicate a predominance of GABA A receptor heteromers containing subunits α2, β1, and/or β3, and γ. Intracellular Ca 2+ 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 GABA A receptors. These data indicate that NPCs derived from human fetal midbrain tissue acquire essential GABA A receptor properties during neuronal maturation in vitro .