Nonsynaptic communication through ATP release from volume-activated anion channels in axons.

Nonsynaptic communication through ATP release from volume-activated anion channels in axons.
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DOI:
10.1126/scisignal.2001128
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发表时间:
2010-10-05
期刊:
影响因子:
7.3
通讯作者:
Ni Y
Ni Y
中科院分区:
生物学1区
文献类型:
--
作者:
Fields RD;Ni Y

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神经元信使在突触外的释放具有广泛的生物学意义,特别是关于轴突和神经胶质之间的通信。我们确定了一种机制,非突触,非囊泡释放三磷酸腺苷(ATP)从轴突通过体积激活阴离子通道(VAAC)激活微观轴突肿胀在动作电位放电。我们结合ATP释放的单光子成像,以及内在光信号、细胞内钙离子(Ca2+)、延时视频和共聚焦显微镜成像,研究了这种神经递质的动作电位诱导的非突触释放。培养的胚胎背根神经节轴突的ATP释放持续巴弗洛霉素或肉毒杆菌毒素被用来阻止囊泡释放,而药理学抑制VAAC或预防动作电位诱导的轴突肿胀抑制ATP释放和破坏轴突和星形胶质细胞之间的活性依赖性信号。这种非囊泡的、非突触的通讯可以介导正常条件下、发育和疾病中轴突和神经系统细胞之间的各种活动依赖性相互作用。
The release of neuronal messengers outside synapses has broad biological implications, particularly with regard to communication between axons and glia. We identify a mechanism for nonsynaptic, nonvesicular release of adenosine triphosphate (ATP) from axons through volume-activated anion channels (VAACs) activated by microscopic axon swelling during action potential firing. We used a combination of single-photon imaging of ATP release, together with imaging for intrinsic optical signals, intracellular calcium ions (Ca2+), time-lapse video, and confocal microscopy, to investigate action potential–induced nonsynaptic release of this neurotransmitter. ATP release from cultured embryonic dorsal root ganglion axons persisted when bafilomycin or botulinum toxin was used to block vesicular release, whereas pharmacological inhibition of VAACs or prevention of action potential–induced axon swelling inhibited ATP release and disrupted activity-dependent signaling between axons and astrocytes. This nonvesicular, nonsynaptic communication could mediate various activity-dependent interactions between axons and nervous system cells in normal conditions, development, and disease.
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发表时间: 2001-08-01
影响因子: 7.3
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