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Photoactivation of an Acid-Sensitive Ion Channel Associated with Vision and Pain
Oliver S Shafaat1, Jay R Winkler1, Harry B Gray2
1Beckman Institute and Division of Chemistry and Chemical Engineering, The California Institute of Technology, 1200 E. California Avenue, Pasadena, CA, 91125, USA.
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.
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