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Development of G Protein-mediated Ca2+ Channel Regulation in Mouse Embryonic Stem Cell-derived Neurons
Besides other mechanisms, the influx of Ca2+ into embryonic neurons controls growth and differentiation processes. To study the expression and regulation of voltage‐gated Ca2+ channels during early neurogenesis, we measured whole‐cell Ca2+ currents (Ica) in neurons developing from pluripotent embryo...
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Published in: | The European journal of neuroscience 1997-04, Vol.9 (4), p.824-832 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Besides other mechanisms, the influx of Ca2+ into embryonic neurons controls growth and differentiation processes. To study the expression and regulation of voltage‐gated Ca2+ channels during early neurogenesis, we measured whole‐cell Ca2+ currents (Ica) in neurons developing from pluripotent embryonic stem cells. Various receptor agonists, including somatostatin and baclofen, reversibly inhibited ICa in embryonic stem cell‐derived neurons. The effects of somatostatin and baclofen were abolished by pretreatment of cells with pertussis toxin and mimicked by intracellular infusion of guanosine 5′‐O‐(3‐thiotriphosphate), suggesting the involvement of pertussis toxin‐sensitive G proteins in Ica inhibition. Investigations at different stages of neuronal differentiation showed that somatostatin efficiently suppressed L‐ and N‐type Ca2+ channels in immature as well as mature neurons. In contrast, inhibition of L‐ and N‐type channels by baclofen was rarely observed at the early stage. In terminally differentiated neurons, responses to baclofen were as prominent as those to somatostatin but were confined to N‐type Ca2+ channels. The stage‐dependent sensitivity of voltage‐gated Ca2+ channels to somatostatin and baclofen was not due to differential expression of Gαo isoforms, as revealed by reverse transcription‐polymerase chain reaction and immunofluorescence microscopy. These findings demonstrate that specific neurotransmitters such as somatostatin regulate voltage‐gated Ca2+ channels via G proteins during the early stages of neurogenesis, thus providing a mechanism for the epigenetic control of neuronal differentiation. |
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ISSN: | 0953-816X 1460-9568 |
DOI: | 10.1111/j.1460-9568.1997.tb01432.x |