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Aim

Neurotransmitter release is elicited by an elevation of intracellular Ca2+ concentration Ca2+i. The action potential triggers Ca2+ influx through Ca2+ channels which causes local changes of Ca2+i for vesicle release. However, any direct role of extracellular Ca2+ besides Ca2+ influx on Ca2+-dependent exocytosis remains elusive. Here we set out to investigate this possibility on rat dorsal root ganglion DRG neurons and chromaffin cells, widely used models for studying vesicle exocytosis.

Results

Using photolysis of caged Ca2+ and caffeine-induced release of stored Ca2+, we found that extracellular Ca2+ inhibited exocytosis following moderate Ca2+i rises 2–3 µM. The IC50 for extracellular Ca2+ inhibition of exocytosis ECIE was 1.38 mM and a physiological reduction ∼30% of extracellular Ca2+ concentration Ca2+o significantly increased the evoked exocytosis. At the single vesicle level, quantal size and release frequency were also altered by physiological Ca2+o. The calcimimetics Mg2+, Cd2+, G418, and neomycin all inhibited exocytosis. The extracellular Ca2+-sensing receptor CaSR was not involved because specific drugs and knockdown of CaSR in DRG neurons did not affect ECIE.

Conclusion-Significance

As an extension of the classic Ca2+ hypothesis of synaptic release, physiological levels of extracellular Ca2+ play dual roles in evoked exocytosis by providing a source of Ca2+ influx, and by directly regulating quantal size and release probability in neuronal cells.



Autor: Wei Xiong , Tao Liu , Yeshi Wang, Xiaowei Chen, Lei Sun, Ning Guo, Hui Zheng, Lianghong Zheng, Martial Ruat, Weiping Han, Claire

Fuente: http://plos.srce.hr/



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