Fathali Hoda, Dunevall Johan, Majdi Soodabeh, Cans Ann-Sofie
Department of Chemistry and Chemical Engineering, Chalmers University of Technology.
Department of Chemistry and Molecular Biology, University of Gothenburg.
J Vis Exp. 2018 Feb 19(132):56537. doi: 10.3791/56537.
Amperometry recording of cells subjected to osmotic shock show that secretory cells respond to this physical stress by reducing the exocytosis activity and the amount of neurotransmitter released from vesicles in single exocytosis events. It has been suggested that the reduction in neurotransmitters expelled is due to alterations in membrane biophysical properties when cells shrink in response to osmotic stress and with assumptions made that secretory vesicles in the cell cytoplasm are not affected by extracellular osmotic stress. Amperometry recording of exocytosis monitors what is released from cells the moment a vesicle fuses with the plasma membrane, but does not provide information on the vesicle content before the vesicle fusion is triggered. Therefore, by combining amperometry recording with other complementary analytical methods that are capable of characterizing the secretory vesicles before exocytosis at cells is triggered offers a broader overview for examining how secretory vesicles and the exocytosis process are affected by osmotic shock. We here describe how complementing amperometry recording with intracellular electrochemical cytometry and transmission electron microscopy (TEM) imaging can be used to characterize alterations in secretory vesicles size and neurotransmitter content at chromaffin cells in relation to exocytosis activity before and after exposure to osmotic stress. By linking the quantitative information gained from experiments using all three analytical methods, conclusions were previously made that secretory vesicles respond to extracellular osmotic stress by shrinking in size and reducing the vesicle quantal size to maintain a constant vesicle neurotransmitter concentration. Hence, this gives some clarification regarding why vesicles, in response to osmotic stress, reduce the amount neurotransmitters released during exocytosis release. The amperometric recordings here indicate this is a reversible process and that vesicle after osmotic shock are refilled with neurotransmitters when placed cells are reverted into an isotonic environment.
对遭受渗透压休克的细胞进行安培测量记录表明,分泌细胞通过降低胞吐活性以及单次胞吐事件中从囊泡释放的神经递质数量来应对这种物理应激。有人提出,排出的神经递质减少是由于细胞在应对渗透压应激时收缩导致膜生物物理性质发生改变,并且假设细胞质中的分泌囊泡不受细胞外渗透压应激的影响。胞吐作用的安培测量记录监测囊泡与质膜融合瞬间从细胞中释放的物质,但在触发囊泡融合之前不提供有关囊泡内容物的信息。因此,将安培测量记录与其他能够在触发细胞胞吐作用之前表征分泌囊泡的互补分析方法相结合,可以更全面地了解分泌囊泡和胞吐过程如何受到渗透压休克的影响。我们在此描述如何将细胞内电化学细胞术和透射电子显微镜(TEM)成像与安培测量记录相结合,以表征嗜铬细胞中分泌囊泡大小和神经递质含量相对于暴露于渗透压应激前后胞吐活性的变化。通过将使用所有三种分析方法从实验中获得的定量信息联系起来,先前得出的结论是,分泌囊泡通过缩小尺寸和降低囊泡量子大小来应对细胞外渗透压应激,以维持恒定的囊泡神经递质浓度。因此,这对囊泡为何在应对渗透压应激时减少胞吐释放过程中释放的神经递质数量给出了一些解释。此处的安培测量记录表明这是一个可逆过程,并且当将遭受渗透压休克后的细胞恢复到等渗环境中时,囊泡会重新充满神经递质。