A light-gated potassium channel for sustained neuronal inhibition
A light-gated potassium channel for sustained neuronal inhibition
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DOI：
10.1038/s41592-018-0186-9
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发表时间：
2018-11-01
期刊：
影响因子：
48
通讯作者：
Moroni, Anna
中科院分区：
文献类型：
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作者：
Alberio, Laura;Locarno, Andrea;Moroni, Anna
目前可用的抑制性光遗传学工具提供了神经元的短暂和瞬时沉默，但由于需要高光强度，它们不能提供持久的抑制。在这里，我们提出了一个优化的蓝光敏感的合成钾通道，BLINK2，它在三个物种的神经元中表现出良好的表达。该通道被低剂量蓝光照射激活，在我们的实验中，它在停止照射后的黑暗中保持活跃（数十）分钟。这种激活引起长时间的抑制神经元放电在离体记录的小鼠神经元和受损的运动神经元反应在斑马鱼体内。作为概念验证应用，我们证明了在自由移动的神经性疼痛大鼠模型中，少量BLINK 2通道的激活引起疼痛感觉的持久（>30分钟）减少。
Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped. This activation caused long periods of inhibition of neuronal firing in ex vivo recordings of mouse neurons and impaired motor neuron response in zebrafish in vivo. As a proof-of-concept application, we demonstrated that in a freely moving rat model of neuropathic pain, the activation of a small number of BLINK2 channels caused a long-lasting (>30 min) reduction in pain sensation.