Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh
Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh
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DOI：
10.1038/nn.2776
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发表时间：
2011-04-01
影响因子：
25
通讯作者：
Bamberg, Ernst
中科院分区：
文献类型：
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作者：
Kleinlogel, Sonja;Feldbauer, Katrin;Bamberg, Ernst
光门控阳离子通道视紫红质-2（ChR 2）已迅速成为神经科学中的重要工具，并且正在考虑将其用于治疗干预。虽然野生型和已知的变体ChR 2能够驱动光激活的尖峰序列，但它们在潜在的临床应用中的使用受到低光敏感性或慢通道动力学的限制。我们提出了一种新的变体，钙转运通道视紫红质（CatCh），它介导了加速的响应时间和电压响应，类似于70倍以上的光敏感性比野生型ChR 2。CatCh的上级性质源于其增强的Ca 2+渗透性。[Ca 2 +]（i）的增加提高了内表面电位，促进电压门控Na+通道的激活，并间接增加了光敏感性。光刺激后的复极化明显加速钙依赖性BK通道激活。我们的研究结果证明了一个以前未知的原则：从一价到二价阳离子转移渗透性，以增加敏感性，而不影响神经元激活的快速动力学。这为光门控通道的临床应用铺平了道路。
The light-gated cation channel channelrhodopsin-2 (ChR2) has rapidly become an important tool in neuroscience, and its use is being considered in therapeutic interventions. Although wild-type and known variant ChR2s are able to drive light-activated spike trains, their use in potential clinical applications is limited by either low light sensitivity or slow channel kinetics. We present a new variant, calcium translocating channelrhodopsin (CatCh), which mediates an accelerated response time and a voltage response that is similar to 70-fold more light sensitive than that of wild-type ChR2. CatCh's superior properties stem from its enhanced Ca2+ permeability. An increase in [Ca2+](i) elevates the internal surface potential, facilitating activation of voltage-gated Na+ channels and indirectly increasing light sensitivity. Repolarization following light-stimulation is markedly accelerated by Ca2+-dependent BK channel activation. Our results demonstrate a previously unknown principle: shifting permeability from monovalent to divalent cations to increase sensitivity without compromising fast kinetics of neuronal activation. This paves the way for clinical use of light-gated channels.