Photoactivation of an Acid-Sensitive Ion Channel Associated with Vision and Pain.
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.
Beckman Institute and Division of Chemistry and Chemical Engineering, The California Institute of Technology, 1200 E. California Avenue, Pasadena, CA, 91125, USA.
Oliver S
0000-0002-3170-2553
OS
Shafaat
Beckman Institute and Division of Chemistry and Chemical Engineering, The California Institute of Technology, 1200 E. California Avenue, Pasadena, CA, 91125, USA.
Jay R
JR
Winkler
Beckman Institute and Division of Chemistry and Chemical Engineering, The California Institute of Technology, 1200 E. California Avenue, Pasadena, CA, 91125, USA. hbgray@caltech.edu.
Harry B
HB
Gray
Beckman Institute and Division of Chemistry and Chemical Engineering, The California Institute of Technology, 1200 E. California Avenue, Pasadena, CA, 91125, USA. dadoc@caltech.edu.
Dennis A
DA
Dougherty
D062565:Acid Sensing Ion Channels / Q000502:physiology / Q000528:radiation effects*; D000818:Animals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D008024:Ligands; D008027:Light; D010146:Pain / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000528:radiation effects; D014785:Vision, Ocular / Q000502:physiology
D062565:Acid Sensing Ion Channels; D008024:Ligands; D011978:Receptors, Nicotinic
acid sensitivity; ion channels; merocyanine; photoactivation