Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.
Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.
复制标题
局部质子瞬变激活酸敏感离子通道揭示了它们在质子信号传导中的作用
DOI：
10.1038/srep14125
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发表时间：
2015-09-15
影响因子：
4.6
通讯作者：
Xu TL
中科院分区：
文献类型：
--
作者：
Zeng WZ;Liu DS;Liu L;She L;Wu LJ;Xu TL
细胞外pH变化的瞬变可能在神经系统中介导信号转导。神经元酸敏感离子通道(ASIC)是细胞外质子的传感器，但ASIC激活的机制在很大程度上仍不清楚。在这里，我们表明，在光激活的质子泵--古紫质-3(Arch)激活后，质子瞬变在共表达ASIC1a通道的神经元和HEK293T细胞中诱导ASIC电流。利用嵌合体蛋白通过甘氨酸/丝氨酸连接物连接Arch和ASIC1a，我们发现成功的偶联发生在15 nm的距离内。此外，两细胞嗅探贴片记录显示，通过Arch或电压门控质子通道Hv1调节质子的释放激活了表达ASIC1a通道的相邻细胞。最后，计算模型预测细胞间界面的峰值质子浓度为pH 6.7，这是足够酸性的，足以在体内激活ASIC。我们的结果强调了质子信号在神经系统中的病理生理学作用。
Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump,Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICsin vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.