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Development of G Protein‐mediated Ca 2+ Channel Regulation in Mouse Embryonic Stem Cell‐derived Neurons
Author(s) -
Strübing Carsten,
Rohwedel Jürgen,
AhnertHilger Gudrun,
Wiedenmann Bertram,
Hescheler Jürgen,
Wobus Anna M.
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01432.x
Subject(s) - pertussis toxin , somatostatin , microbiology and biotechnology , embryonic stem cell , biology , neurogenesis , cellular differentiation , chemistry , endocrinology , signal transduction , g protein , biochemistry , gene
Besides other mechanisms, the influx of Ca 2+ into embryonic neurons controls growth and differentiation processes. To study the expression and regulation of voltage‐gated Ca 2+ channels during early neurogenesis, we measured whole‐cell Ca 2+ currents (I ca ) in neurons developing from pluripotent embryonic stem cells. Various receptor agonists, including somatostatin and baclofen, reversibly inhibited I Ca 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 I ca inhibition. Investigations at different stages of neuronal differentiation showed that somatostatin efficiently suppressed L‐ and N‐type Ca 2+ 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 Ca 2+ channels. The stage‐dependent sensitivity of voltage‐gated Ca 2+ channels to somatostatin and baclofen was not due to differential expression of Gα o isoforms, as revealed by reverse transcription‐polymerase chain reaction and immunofluorescence microscopy. These findings demonstrate that specific neurotransmitters such as somatostatin regulate voltage‐gated Ca 2+ channels via G proteins during the early stages of neurogenesis, thus providing a mechanism for the epigenetic control of neuronal differentiation.