Photo-modulated ion channels based on covalently linked gramicidins.
The covalent coupling of two gramicidin A monomers proved to be a useful tool for the rational design of ion channels with predictable electrophysiological properties (Stankovic, C.J., Heinemann, S.H., Delfino, J.M., Sigworth, F.J. and Schreiber, S.L. (1989) Science 244, 813-817; Stankovic, C.J., Heinemann, S.H. and Schreiber, S.L. (1990) J. Am. Chem. Soc. 112, 3702-3704). Herein we report on our first efforts to equip such channels with an artificial gating mechanism. Gramicidin monomers were covalently linked with 3,3'-azobis(benzeneacetic acid). Based on computer modeling of the beta-helix channel motif, this linker in its dark-adapted (trans) form does not allow for the formation of unimolecular ion channels, while the photo-activated (cis) form was expected to provide this possibility. The electrophysiological assays showed that (A) the trans-isomer does form characteristic ion channels, and (B) irradiation transforms these channels into a new distinct, flickering channel type in a reversible manner. The results are discussed in the framework of intermolecular gramicidin aggregates.
Stankovic
C J
CJ
Department of Chemistry, Harvard University, Cambridge, MA.
Heinemann
S H
SH
Schreiber
S L
SL
D001391:Azo Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006096:Gramicidin / Q000493:pharmacokinetics*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008027:Light; D008051:Lipid Bilayers / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D010648:Phenylacetates / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D001391:Azo Compounds; D007473:Ion Channels; D008051:Lipid Bilayers; D010648:Phenylacetates; C067674:3,3'-azobis(benzeneacetic acid); D006096:Gramicidin; D004121:Dimethyl Sulfoxide