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Ca2+ and cAMP Signaling in Human Embryonic Stem Cell-Derived Dopamine Neurons
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2010 (English)In: Stem Cells and Development, ISSN 1547-3287, Vol. 19, no 9, 1355-1364 p.Article in journal (Refereed) Published
Abstract [en]

Human embryonic stem (hES) cell differentiation into dopamine neurons is considered a promising strategy for cell replacement therapy in Parkinson's disease, yet the functional properties of hES cell-derived dopamine neurons remain poorly defined. The objective of this study was to characterize intracellular calcium (Ca2+)and sub-plasma membrane cyclic AMP-signaling properties in hES cell-derived dopamine neurons. We found that hES cell-derived dopamine neurons and neural progenitors raised Ca2+ from intra-and extracellular compartments in response to depolarization, glutamate, ATP,and dopamine D-2 receptor activation, while undifferentiated hES cells only mobilized Ca2+ from intracellular stores in response to ATP and D 2 receptor-induced activation. Interestingly, we also found that hES cell-derived dopamine neurons in addition to primary ventral midbrain dopamine neurons were more prone to release Ca2+ from intracellular stores than non-dopamine neurons following treatment with the neuropeptide neurotensin. Furthermore, hES cell-derived dopamine neurons showed cAMP elevations in response to forskolin and 3-isobutyl-methylxanthine, similar to primary dopamine neurons. Taken together, these results unravel the temporal sequence by which hES cells acquire Ca2+ and cAMP signaling competence during dopamine differentiation.

Place, publisher, year, edition, pages
2010. Vol. 19, no 9, 1355-1364 p.
National Category
Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-134906DOI: 10.1089/scd.2009.0436ISI: 000281517700008OAI: oai:DiVA.org:uu-134906DiVA: diva2:374041
Available from: 2010-12-02 Created: 2010-12-02 Last updated: 2010-12-02Bibliographically approved

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