Tuning Photochromic Ion Channel Blockers

被引:136
作者
Mourot, Alexandre [2 ]
Kienzler, Michael A. [1 ,3 ,4 ]
Banghart, Matthew R. [3 ]
Fehrentz, Timm [1 ,4 ]
Huber, Florian M. E. [1 ,4 ]
Stein, Marco [1 ,4 ]
Kramer, Richard H. [2 ]
Trauner, Dirk [1 ,4 ]
机构
[1] Univ Munich, Dept Chem & Pharmacol, Munich, Germany
[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[4] Ctr Integrated Prot Sci, D-81377 Munich, Germany
来源
ACS CHEMICAL NEUROSCIENCE | 2011年 / 2卷 / 09期
基金
美国国家卫生研究院;
关键词
photopharmacology; ion channel blockers; voltage-gated potassium channels; photochromic molecules; azobenzenes; PURKINJE-CELLS; REMOTE-CONTROL; GLUTAMATE; MECHANISMS; AGONIST;
D O I
10.1021/cn200037p
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Photochromic channel blockers provide a conceptually simple and convenient way to modulate neuronal activity with light. We have recently described a family of azobenzenes that function as tonic blockers of K-v channels but require UV-A light to unblock and need to be actively switched by toggling between two different wavelengths. We now introduce red-shifted compounds that fully operate in the visible region of the spectrum and quickly turn themselves off in the dark. Furthermore, we have developed a version that does not block effectively in the dark-adapted state, can be switched to a blocking state with blue light, and reverts to the inactive state automatically. Photochromic blockers of this type could be useful for the photopharmacological control of neuronal activity under mild conditions.
引用
收藏
页码:536 / 543
页数:8
相关论文
共 25 条
[1]   A signal processing analysis of Purkinje cells in vitro [J].
Abrams, Ze'ev R. ;
Warrier, Ajithkumar ;
Trauner, Dirk ;
Zhang, Xiang .
FRONTIERS IN NEURAL CIRCUITS, 2010, 4
[2]   Light-activated ion channels for remote control of neuronal firing [J].
Banghart, M ;
Borges, K ;
Isacoff, E ;
Trauner, D ;
Kramer, RH .
NATURE NEUROSCIENCE, 2004, 7 (12) :1381-1386
[3]   Engineering light-gated ion channels [J].
Banghart, Matthew R. ;
Volgraf, Matthew ;
Trauner, Dirk .
BIOCHEMISTRY, 2006, 45 (51) :15129-15141
[4]   Photochromic Blockers of Voltage-Gated Potassium Channels [J].
Banghart, Matthew R. ;
Mourot, Alexandre ;
Fortin, Doris L. ;
Yao, Jennifer Z. ;
Kramer, Richard H. ;
Trauner, Dirk .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (48) :9097-9101
[5]   PHOTOCHROMIC ACTIVATORS OF ACETYLCHOLINE RECEPTOR [J].
BARTELS, E ;
WASSERMANN, NH ;
ERLANGER, BF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1971, 68 (08) :1820-+
[6]   Light-induced depolarization of neurons using a modified Shaker K+ channel and a molecular photoswitch [J].
Chambers, James J. ;
Banghart, Matthew R. ;
Trauner, Dirk ;
Kramer, Richard H. .
JOURNAL OF NEUROPHYSIOLOGY, 2006, 96 (05) :2792-2796
[7]  
Deisseroth K, 2011, NAT METHODS, V8, P26, DOI [10.1038/nmeth.f.324, 10.1038/NMETH.F.324]
[8]  
Fortin DL, 2008, NAT METHODS, V5, P331, DOI [10.1038/NMETH.1187, 10.1038/nmeth.1187]
[9]   Optical switches for remote and noninvasive control of cell signaling [J].
Gorostiza, Pau ;
Isacoff, Ehud Y. .
SCIENCE, 2008, 322 (5900) :395-399
[10]   Mechanisms of photoswitch conjugation and light activation of an ionotropic glutamate receptor [J].
Gorostiza, Pau ;
Volgraf, Matthew ;
Numano, Rika ;
Szobota, Stephanie ;
Trauner, Dirk ;
Isacoff, Ehud Y. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (26) :10865-10870