Premium
Enhanced maturation of induced pluripotent stem (iPS) cell‐derived neurons by astrocyte‐conditioned medium: roles of differential regulation of Ca2+ channel and GABAA receptor activities
Author(s) -
Rushton David James,
Mattis Virginia B,
Svendsen Clive N,
Arjomand Jamshid,
Allen Nick D,
Kemp Paul J
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1126.2
Subject(s) - synaptogenesis , depolarization , astrocyte , neuroscience , gabaa receptor , microbiology and biotechnology , neurogenesis , hyperpolarization (physics) , biology , chemistry , premovement neuronal activity , receptor , biophysics , biochemistry , central nervous system , organic chemistry , nuclear magnetic resonance spectroscopy
Astrocytes promote synaptogenesis in vitro , a development which may be crucial to generating appropriate stem cell derived models of neurodegenerative diseases. However, the mechanism(s) by which they exert such effects are currently unknown. We investigated the influence of mouse striatal astrocyte conditioned medium, at 7, 14 and 21 days, on the differentiation and maturation of human iPS‐derived neuroprogenitors using whole‐cell patch‐clamp and Ca 2+ imaging. Although the proportion of cells able to fire an action potential in response to depolarization was unaffected, the conditioned medium evoked: i) significant hyperpolarization of the membrane at rest; ii) upregulation of L‐, N‐ and R‐ type Ca 2+ channel function, and; iii) a dramatic increase in the proportion of spontaneously active cells. Increasing the extracellular [Ca 2+ ] from 0.6 to 1.8 mM resulted in accelerated neurogenesis and mimicked the enhanced maturity seen with astrocyte conditioned medium. These effects were blocked using specific inhibition of N‐ and L‐ type Ca 2+ channels or GABA A receptors. Taken together, these data demonstrate a clear role for GABA A ‐evoked depolarization, and consequent voltage‐gated Ca 2+ influx, in the process of neuronal maturation, and suggest that astrocytes may promote synaptogenesis, at least in part, via increased gain of the GABA excitation pathway. Funded by MRC and CHDI.