The effect of free radicals on the conductance induced by alamethicin in planar lipid membranes: activation and inactivation.
Exposure to ionizing radiation of planar lipid membranes doped with alamethicin gives rise to an increase and to a subsequent decrease of the membrane conductance. Both effects are due to the presence of radiation-induced free radicals of water radiolysis as was shown by addition of various radical scavengers. The increase of the conductance was found to be a consequence of free radical-initiated lipid peroxidation favouring the formation of active ion channels. The decrease of the conductance observed at larger radiation doses is due to an inactivation of alamethicin monomers. The characteristic D37 dose of inactivation was found to be about two orders of magnitude larger than in the case of gramicidin A. The comparatively high sensitivity of the latter is due to the presence of its four tryptophan residues. Inactivation of trichorzianine AIIIc, an analogue of alamethicin with a C-terminal tryptophanol residue, occurs at radiation doses two orders of magnitude lower than observed with alamethicin.
Zeidler
U
U
Department of Biology, University of Konstanz, Germany.
Wilhelm
M
M
Stark
G
G
D000408:Alamethicin / Q000494:pharmacology*; D000595:Amino Acid Sequence; D002712:Chlorides / Q000494:pharmacology; D004553:Electric Conductivity; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology*; D007700:Kinetics; D008081:Liposomes; D008969:Molecular Sequence Data; D013431:Sulfates / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*; D014965:X-Rays
D002712:Chlorides; D016166:Free Radical Scavengers; D005609:Free Radicals; D007476:Ionophores; D008081:Liposomes; D013431:Sulfates; D013481:Superoxides; D000408:Alamethicin; D017665:Hydroxyl Radical