Light-activated ion channels for remote control of neuronal firing
Light-activated ion channels for remote control of neuronal firing
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DOI：
10.1038/nn1356
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发表时间：
2004-12-01
影响因子：
25
通讯作者：
Kramer, RH
中科院分区：
文献类型：
--
作者：
Banghart, M;Borges, K;Kramer, RH
神经元具有直接由电压、配体和温度而不是由光门控的离子通道。使用基于结构的设计，我们已经开发出一种新的化学门，赋予光敏感性的离子通道。所述门包括用于选择性缀合至工程化K+通道的官能团、孔阻断剂和可光异构化偶氮苯。长波长的光驱动偶氮苯部分进入其扩展的反式构型，允许阻断剂到达孔。短波长的光产生较短的顺式构型，使阻断剂缩回并允许传导。这些通道在大鼠海马神经元中的外源性表达，然后用光开关门进行化学修饰，使不同波长的光能够打开和关闭动作电位。这些合成的可光异构化的偶氮苯调节的K+（SPARK）通道允许对神经元放电进行快速、精确和可逆的控制，具有用于解剖神经回路和控制神经损伤或变性位点下游的活性的潜在应用。
Neurons have ion channels that are directly gated by voltage, ligands and temperature but not by light. Using structure-based design, we have developed a new chemical gate that confers light sensitivity to an ion channel. The gate includes a functional group for selective conjugation to an engineered K+ channel, a pore blocker and a photoisomerizable azobenzene. Long-wavelength light drives the azobenzene moiety into its extended trans configuration, allowing the blocker to reach the pore. Short-wavelength light generates the shorter cis configuration, retracting the blocker and allowing conduction. Exogenous expression of these channels in rat hippocampal neurons, followed by chemical modification with the photoswitchable gate, enables different wavelengths of light to switch action potential firing on and off. These synthetic photoisomerizable azobenzene-regulated K+ (SPARK) channels allow rapid, precise and reversible control over neuronal firing, with potential applications for dissecting neural circuits and controlling activity downstream from sites of neural damage or degeneration.