An Inhibitory Effect of Extracellular Ca2+ on Ca2+-Dependent Exocytosis

作者：Xiong, Wei^*; Liu, Tao; Wang, Yeshi; Chen, Xiaowei; Sun, Lei; Guo, Ning; Zheng, Hui; Zheng, Lianghong; Ruat, Martial; Han, Weiping; Zhang, Claire Xi; Zhou, Zhuan

来源：PLos One, 2011, 6(10): e24573.

DOI：10.1371/journal.pone.0024573

• ADRENAL CHROMAFFIN CELLS
• ROOT GANGLION NEURONS
• CALCIUM-SENSING RECEPTOR
• SYNAPTIC VESICLE EXOCYTOSIS
• TRANSMITTER RELEASE
• CA2+-SENSING RECEPTOR
• CATION CHANNEL
• NEUROTRANSMITTER RELEASE
• PRESYNAPTIC CALCIUM
• HIPPOCAMPAL-NEURONS

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 Ca 2+ and caffeine-induced release of stored Ca2+, we found that extracellular Ca2+ inhibited exocytosis following moderate [Ca2+](i) rises (2-3 mM). The IC50 for extracellular Ca2+ inhibition of exocytosis (ECIE) was 1.38 mM and a physiological reduction (similar to 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.

• 出版日期2011-10-18
• 单位北京大学