摘 要：摘 要：星型胶质细胞虽然没有动作电位，但是可以表达多种受体和离子通道，并且以细胞内钙波传递的方式来响应各类刺激。星型胶质细胞同样可以释放多种信号分子来介导细胞间的通讯。尤为特别的是，星型胶质细胞的钙波传播和突触功能的反馈调节都需要其释放ATP才得以完成。然而，星型胶质细胞释放ATP的途径和机理还有待研究。尽管人们已经在星型胶质细胞中发现了小囊泡和大致密核心囊泡的标记物，可是用以胞吐的囊泡究竟是什么还并不清楚。作者等近期的研究成果表明，FM染料棗一种被成功应用于研究神经元和其他分泌型细胞囊泡循环的染料，可以特异地标记星型胶质细胞的溶酶体，并依不同程度的刺激表现出两种不同模式的钙离子依赖性胞吐：在较低强度刺激下（ATP, 谷氨酸）发生部分胞吐，而在高强度刺激下（氰化钾）则发生完全胞吐。进一步研究表明，溶酶体中含有大量ATP，并且在部分胞吐时少量释放ATP，完全胞吐时大量释放ATP，同时释放溶酶体酶。选择性地裂解星型胶质细胞的溶酶体，发现ATP释放和钙波传播都消失了。总之，星型胶质细胞的溶酶体可以通过调节性胞吐对生理和病理条件下的细胞间信号传递产生重要意义。
关键词：ATP；溶酶体；星型胶质细胞
中图分类号：Q25; Q421 文献标识码：A
Abstract: Abstract：Although lacking action potentials, astrocytes express various receptors and ion channels and exhibit intercellular propagating Ca2+ waves in response to various stimuli. Astrocytes can also release many signal molecules that mediate intercellular communication. In particular, ATP release from astrocytes is required for Ca2+ wave propagation among astrocytes and for feedback modulation of synaptic functions. However, the mechanisms and the source of ATP release from astrocytes remain to be established. Although markers for both small vesicles and large dense core vesicles are found in astrocytes, the identity of vesicles undergoing exocytosis has been largely unclear. In the present study, we found that lysosomes in astrocytes can be specifically labeled with FM dyes, which have been successfully used for studying vesicle recycling in neurons and secretory cells, and exhibit two modes of Ca2+-dependent exocytosis - partial release in response to mild extracellular stimuli (ATP, glutamate) and full release triggered by the ischemic insult (potassium cyanide, KCN). Further studies showed that lysosomes contain abundant ATP and their partial exocytosis resulted in a low-level ATP release, whereas full exocytosis led to the release of a larger amount of ATP, together with lysosomal enzymes. Selective intracellular lysis of lysosomes abolished both ATP release and Ca2+ wave propagation among astrocytes. Together, these findings indicate that regulated lysosome release from astrocytes contribute to intercellular signaling under physiological as well as pathological conditions.
Key words：ATP；lysosome；astrocyte
