Abstract
Potential step amperometry (chronoamperometry) of the Tl(I)/Tl(Hg) electrochemical reduction process has been used to investigate the underlying mechanisms of gramicidin activity in phospholipid monolayers. The experiments were carried out at gramicidin-modified dioleoyl phosphatidylcholine (DOPC)-coated electrodes. Application of a potential step to the coated electrode system results in a current transient that can be divided into two regions. An initial exponential decay of current corresponds to the inactivation of monomer channel conductance and a longer time scale quasi-steady-state represents the diffusion of ions to a bimolecular surface reaction. Concentrations of monomer conducting channels are relatively low, and the results indicate that two or more forms of gramicidin are in equilibrium with each other in the layer. Aromatic/conjugated compounds incorporated into the monolayer increase the reduction current by decreasing the rate of channel inactivation and increasing the stability of the conducting channel. This effect is positively correlated with the degree of the compound's aromaticity. The anomalous influence of alkali metal ions on the reduction current is consistent with the model of gramicidin being speciated in the monolayer in more than one form. The results have implications on the lability of the peptide conformation in biological membranes and its dependence on lipid environment, solution composition, and applied potential.