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与视觉和疼痛相关的酸敏感离子通道的光激活

Photoactivation of an Acid-Sensitive Ion Channel Associated with Vision and Pain.

作者信息

Shafaat Oliver S, Winkler Jay R, Gray Harry B, Dougherty Dennis A

机构信息

Beckman Institute and Division of Chemistry and Chemical Engineering, The California Institute of Technology, 1200 E. California Avenue, Pasadena, CA, 91125, USA.

出版信息

Chembiochem. 2016 Jul 15;17(14):1323-7. doi: 10.1002/cbic.201600230. Epub 2016 Jun 2.

Abstract

We describe the reversible photoactivation of the acid sensitive ligand-gated ion channel ASIC2a, a mammalian channel found throughout the central and peripheral nervous systems that is associated with vision and pain. We also show the activation of GLIC, an acid-sensitive prokaryotic homologue of the nicotinic acetylcholine receptor. Photoactivation was achieved by using visible light irradiation of a newly synthesized water-soluble merocyanine photoacid, 1, which was designed to remove adverse channel blocking effects of a related system. Activation of ASIC2a and GLIC occurs reversibly, in a benign manner, and only upon irradiation. Further studies using transient absorption spectroscopy showed that protonation of a colorimetric base occurred rapidly (ca. 100 μs) after excitation of 1. These results demonstrate that irradiation of 1 can induce rapid, local pH changes that can be used to investigate both biological and chemical proton transfer reactions.

摘要

我们描述了酸敏感配体门控离子通道ASIC2a的可逆光激活,ASIC2a是一种在中枢和外周神经系统中均有发现的哺乳动物通道,与视觉和疼痛相关。我们还展示了GLIC的激活,GLIC是烟碱型乙酰胆碱受体的一种酸敏感原核同源物。通过对新合成的水溶性部花青光酸1进行可见光照射实现了光激活,该光酸旨在消除相关系统的不良通道阻断效应。ASIC2a和GLIC的激活以良性方式可逆发生,且仅在照射时发生。使用瞬态吸收光谱的进一步研究表明,在1激发后,比色碱的质子化迅速发生(约100微秒)。这些结果表明,对1的照射可诱导快速的局部pH变化,可用于研究生物和化学质子转移反应。

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