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.