Center for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada H3G 1A4.
J Neurosci. 2012 Sep 5;32(36):12518-27. doi: 10.1523/JNEUROSCI.1380-12.2012.
Cells can release the free amino acid taurine through volume-regulated anion channels (VRACs), and it has been hypothesized that taurine released from glial cells is capable of inhibiting action potential (AP) firing by activating neuronal glycine receptors (GlyRs) (Hussy et al., 1997). Although an inhibitory GlyR tone is widely observed in the brain, it remains unknown whether this specifically reflects gliotransmission because most neurons also express VRACs and other endogenous molecules can activate GlyRs. We found that VRACs are absent in neurons of the rat supraoptic nucleus (SON), suggesting that glial cells are the exclusive source of taurine in this nucleus. Application of strychnine to rat hypothalamic explants caused a depolarization of SON neurons associated with a decrease of chloride conductance and could excite these cells in the absence of fast synaptic transmission. This inhibitory GlyR tone was eliminated by pharmacological blockade of VRACs, by cellular taurine depletion, by metabolic inactivation of glia with fluorocitrate, and after retraction of astrocytic processes that intercalate neuronal somata and dendrites. Finally, GlyR tone varied inversely with extracellular fluid tonicity to mediate the osmotic control of AP firing by SON neurons. These findings establish taurine as a physiological gliotransmitter and show that gliotransmission is a spatially constrained process that can be modulated by the morphological rearrangement of astrocytes.
细胞可以通过体积调节阴离子通道 (VRAC) 释放游离氨基酸牛磺酸，并且有人假设，星形胶质细胞释放的牛磺酸能够通过激活神经元甘氨酸受体 (GlyRs) 来抑制动作电位 (AP) 放电 (Hussy 等人，1997 年)。尽管在大脑中广泛观察到抑制性 GlyR 张力，但尚不清楚这是否专门反映了神经胶质传递，因为大多数神经元也表达 VRAC 并且其他内源性分子可以激活 GlyRs。我们发现，大鼠视上核 (SON) 的神经元中不存在 VRAC，这表明星形胶质细胞是该核中牛磺酸的唯一来源。用士的宁处理大鼠下丘脑外植体可引起 SON 神经元去极化，与氯离子电导降低相关，并可在没有快速突触传递的情况下兴奋这些细胞。这种抑制性 GlyR 张力被 VRAC 的药理学阻断、细胞内牛磺酸耗竭、用氟柠檬酸使胶质代谢失活以及星形胶质细胞突起缩回后消除，这些突起插入神经元胞体和树突。最后，GlyR 张力与细胞外液渗透压呈反比变化，介导 SON 神经元 AP 放电的渗透控制。这些发现确立了牛磺酸作为一种生理神经胶质递质，并表明神经胶质传递是一种空间受限的过程，可以通过星形胶质细胞的形态重排来调节。
