Potassium channel-based optogenetic silencing.
Potassium channel-based optogenetic silencing.
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DOI：
10.1038/s41467-018-07038-8
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发表时间：
2018-11-05
影响因子：
16.6
通讯作者：
Schmitz D
中科院分区：
文献类型：
--
作者：
Bernal Sierra YA;Rost BR;Pofahl M;Fernandes AM;Kopton RA;Moser S;Holtkamp D;Masala N;Beed P;Tukker JJ;Oldani S;Bönigk W;Kohl P;Baier H;Schneider-Warme F;Hegemann P;Beck H;Seifert R;Schmitz D
光遗传学能够以高时空分辨率利用光来操纵生物过程，以控制细胞、网络甚至整个动物的行为。与兴奋性视紫红质的性能相比，抑制性光遗传学工具的有效性仍然不足。在这里，我们报道了一种由光激活腺苷酸环化酶（PAC）和小环核苷酸门控钾通道 SthK 组成的双组分光学消声器系统。通过低强度蓝光的短暂脉冲激活这种“PAC-K”消音器，会导致心肌细胞兴奋和神经元放电的强烈且可逆的沉默。小鼠和斑马鱼神经元中 PAC-K 的体内表达具有良好的耐受性，蓝光会抑制神经元活动并阻止运动反应。与红光吸收通道视紫红质相结合，PAC 独特的作用光谱可以实现对神经元活动的独立双模式控制。 PAC-K 是一种可靠的光遗传学消音器，具有内在放大作用，可实现持续钾介导的超极化，赋予感兴趣的细胞高操作光敏感性。光遗传学工具可以对细胞行为进行精确的实验控制。在这里，作者介绍了一种基因编码的双蛋白系统，该系统能够使用蓝光沉默神经元和心肌细胞等可兴奋细胞，并证明其在体外和体内的实用性。
Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer system comprising photoactivated adenylyl cyclases (PACs) and the small cyclic nucleotide-gated potassium channel SthK. Activation of this ‘PAC-K’ silencer by brief pulses of low-intensity blue light causes robust and reversible silencing of cardiomyocyte excitation and neuronal firing. In vivo expression of PAC-K in mouse and zebrafish neurons is well tolerated, where blue light inhibits neuronal activity and blocks motor responses. In combination with red-light absorbing channelrhodopsins, the distinct action spectra of PACs allow independent bimodal control of neuronal activity. PAC-K represents a reliable optogenetic silencer with intrinsic amplification for sustained potassium-mediated hyperpolarization, conferring high operational light sensitivity to the cells of interest. Optogenetic tools enable precise experimental control of the behaviour of cells. Here, the authors introduce a genetically-encoded two-protein system that enables silencing of excitable cells such as neurons and cardiomyocytes using blue light, and demonstrate its utility both in vitro and In vivo.
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影响因子：
3.6
作者：
Choi JH;Yu NK;Baek GC;Bakes J;Seo D;Nam HJ;Baek SH;Lim CS;Lee YS;Kaang BK
通讯作者：
Kaang BK
影响因子：
25
作者：
Dombeck, Daniel A.;Harvey, Christopher D.;Tian, Lin;Looger, Loren L.;Tank, David W.
通讯作者：
Tank, David W.
影响因子：
25
作者：
Banghart, M;Borges, K;Kramer, RH
通讯作者：
Kramer, RH
影响因子：
2.5
作者：
Fortin, Doris L.;Dunn, Timothy W.;Kramer, Richard H.
通讯作者：
Kramer, Richard H.
影响因子：
64.8
作者：
Iseki, M;Matsunaga, S;Watanabe, M
通讯作者：
Watanabe, M