Intracellular Uncaging of cGMP with Blue Light

Intracellular Uncaging of cGMP with Blue Light
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DOI:
10.1021/acschemneuro.7b00237
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发表时间:
2017-10-01
影响因子:
5
通讯作者:
Ellis-Davies, Graham C. R.
Ellis-Davies, Graham C. R.
中科院分区:
医学3区
文献类型:
--
作者:
Agarwal, Hitesh K.;Zhai, Shenyu;Ellis-Davies, Graham C. R.

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我们制作了一种新的笼式 cGMP,可以用蓝光进行光解。使用我们最近开发的 7-二乙氨基香豆素 (DEAC) 衍生物(称为 DEAC450),我们合成了 cGMP 香豆素磷酸酯衍生物,DEAC450 部分带有两个负电荷。 DEAC450-cGMP 可易溶于生理缓冲液,无需任何有机共溶剂。 DEAC450-cGMP在453 nm处的光解量子产率为0.18,消光系数为43 000 M-1 cm(-1),是迄今为止最光敏的笼式cGMP。在急性分离脑切片中的膜片钳神经元中,蓝光有效地从 DEAC450 中释放 cGMP,并促进胆碱能中间神经元中超极化和环核苷酸门控阳离子 (HCN) 通道的激活。因此,DEAC450-cGMP 具有一组独特的光学和化学特性,使其成为神经生物学家可用的光学武器库的有用补充。
We have made a new caged cGMP that is photolyzed with blue light. Using our recently developed derivative of 7-diethylaminocourmarin (DEAC) called DEAC450, we synthesized coumarin phosphoester derivatives of cGMP with two negative charges appended to the DEAC450 moiety. DEAC450-cGMP is freely soluble in physiological buffer without the need for any organic cosolvents. With a photolysis quantum yield of 0.18 and an extinction coefficient of 43 000 M-1 cm(-1) at 453 nm, DEAC450-cGMP is the most photosensitive caged cGMP made to date. In patch-clamped neurons in acutely isolated brain slices, blue light effectively uncaged cGMP from DEAC450 and facilitated activation of hyperpolarization and cyclic nucleotide gated cation (HCN) channels in cholinergic interneurons. Thus, DEAC450-cGMP has a unique set of optical and chemical properties that make it a useful addition to the optical arsenal available to neurobiologists.