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Mol Cell Neurosci. 2000 Oct;16(4):376-87.

Specific frequencies of spontaneous Ca2+ transients upregulate GAD 67 transcripts in embryonic spinal neurons.

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Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.


Spontaneous Ca2+ transients expressed prior to synaptogenesis regulate the developmental appearance of GABA in cultured Xenopus spinal neurons. We find that glutamic acid decarboxylase (GAD) immunoreactivity is also Ca(2+)-dependent and parallels the appearance of GABA. We show that xGAD 67 transcripts first appear in the embryonic spinal cord during the period in which these Ca2+ spikes are generated, in a pattern that is temporally and spatially appropriate to account for differentiation of GABAergic interneurons. RNase protection and competitive quantitative RT-PCR demonstrate that transcript levels are approximately threefold greater when neurons are cultured in the presence of extracellular Ca2+ that permits generation of transients than when cultured in its absence. The frequency of spontaneous Ca2+ spikes plays a crucial role in the regulation of transcripts, since reimposition of Ca2+ transients at the frequency generated in cultured neurons rescues normal expression. We conclude that naturally occurring low frequencies of these Ca2+ transients regulate levels of xGAD 67 mRNA in differentiating neurons.

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