Kato Fusao, Imura Taiko, Shigetomi Eiji
Laboratory of Neurophysiology, Department of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2007 Jun;27(3):117-26.
The fast and precise neuron-to-neuron signalling at the synapses is one of the most crucial processes in the central nervous system (CNS) function. Recent advances in the functional and morphological analysis of the brain synapses have identified adenosine 5'-triphosphate (ATP), a ubiquitous and most important molecule in the intracellular functions, to play important roles also as an extracellular messenger at synapses. Lines of evidence accumulated until today indicate that ATP (1) is released into the extracellular space particularly from astrocytes through specific mechanisms, (2) activates specific receptors for extracellular ATP, which modifies synaptic transmission, and (3) is hydrolysed to adenosine by ecto-nucleotidases, which in turn activates specific adenosine receptors modulating synaptic transmission. We have recently shown, using the patch-clamp recording of postsynaptic membrane currents in the acute brain slice preparations in vitro, that (1) ATP activates ATP-gated Ca2+ -permeable channels (P2X receptor channels) on presynaptic terminal membrane, triggering glutamate release without action potential, and (2) adenosine, produced from ATP in the extracellular milieu, activates presynaptic G protein-coupled receptors, which reduces Ca2+ entry through voltage-dependent Ca2+ channels and suppresses action potential-dependent transmitter release. These distinct mechanisms operate in synergy in various CNS structures and form the "purinergic regulatory complex" of the synaptic transmission.
突触处快速且精确的神经元间信号传递是中枢神经系统(CNS)功能中最为关键的过程之一。脑突触功能和形态分析方面的最新进展已确定,三磷酸腺苷(ATP)这种在细胞内功能中普遍存在且最为重要的分子,在突触处作为细胞外信使也发挥着重要作用。直至今日积累的一系列证据表明,ATP:(1)通过特定机制尤其从星形胶质细胞释放到细胞外空间;(2)激活细胞外ATP的特定受体,从而改变突触传递;(3)被胞外核苷酸酶水解为腺苷,腺苷进而激活特定的腺苷受体来调节突触传递。我们最近利用体外急性脑片制备中突触后膜电流的膜片钳记录表明:(1)ATP激活突触前终末膜上的ATP门控Ca²⁺ 通透通道(P2X受体通道),在无动作电位的情况下触发谷氨酸释放;(2)细胞外环境中由ATP产生的腺苷激活突触前G蛋白偶联受体,这会减少通过电压依赖性Ca²⁺ 通道的Ca²⁺ 内流,并抑制动作电位依赖性递质释放。这些不同的机制在各种CNS结构中协同作用,形成突触传递的“嘌呤能调节复合体”。