Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo, 153-8902, Japan.
Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Biochem Biophys Res Commun. 2018 Jul 2;501(4):988-995. doi: 10.1016/j.bbrc.2018.05.097. Epub 2018 May 24.
Astrocytes, a large population of glial cells, detect neurotransmitters and respond by increasing intracellular Ca concentration ([Ca]) and releasing chemical molecules called gliotransmitters. Recently discovered Ca influx through transient receptor potential ankyrin 1 (TRPA1) channels is reported to cause spontaneous [Ca] increase in astrocytes. While several physiological functions of TRPA1-mediated spontaneous Ca signal have been revealed, relation with gliotransmitter release, especially peptide hormone exocytosis is largely unknown. We therefore explored the [Ca] and exocytosis dynamics in rat astrocyte cell line C6 cells and primary astrocytes. TRPA1-mediated spontaneous [Ca] transients were observed in both C6 cells and primary astrocytes. Total internal reflection fluorescence microscopy revealed that Venus-tagged brain-derived neurotrophic factor and neuropeptide Y were released spontaneously from astrocytes. Activation of TRPA1 channels enhanced the frequency of peptide hormone exocytosis, and inhibition of TRPA1 channels decreased the number of peptide hormone exocytosis. These results suggest that TRPA1-mediated spontaneous [Ca] increase modulates the spontaneous release of peptide hormones from astrocytes.
星形胶质细胞是一大类神经胶质细胞，它们可以检测神经递质，并通过增加细胞内 Ca 浓度 ([Ca]) 和释放称为神经递质的化学分子来做出反应。最近发现，通过瞬时受体电位锚蛋白 1（TRPA1）通道的 Ca 内流会导致星形胶质细胞中自发的 [Ca]增加。虽然已经揭示了 TRPA1 介导的自发 Ca 信号的几种生理功能，但与神经递质释放的关系，特别是肽激素胞吐作用，在很大程度上尚不清楚。因此，我们探索了大鼠星形胶质细胞系 C6 细胞和原代星形胶质细胞中的 [Ca]和胞吐动力学。在 C6 细胞和原代星形胶质细胞中均观察到 TRPA1 介导的自发 [Ca]瞬变。全内反射荧光显微镜显示，来自星形胶质细胞的 Venus 标记的脑源性神经营养因子和神经肽 Y 自发释放。TRPA1 通道的激活增强了肽激素胞吐作用的频率，而 TRPA1 通道的抑制减少了肽激素胞吐作用的数量。这些结果表明，TRPA1 介导的自发 [Ca]增加调节了星形胶质细胞中肽激素的自发释放。
