Can Ag(+) Permeate through a Potassium Ion Channel? A Bottom-Up Approach by Infrared Spectroscopy of the Ag(+) Complex with the Partial Peptide of a Selectivity Filter

[Image: see text] Silver and silver ions have a long history of antimicrobial activity and medical applications. Nevertheless, the activity of Ag(+) against bacteria, how it enters a cell, has not yet been established. The K(+) channel, a membrane protein, is a possible route. The addition of a channel inhibitor (4-aminopyridine) to modulate the Ag(+) uptake could support this view. However, the inhibitor enhances the uptake of Ag(+), the opposite result. We have applied cold ion trap infrared laser spectroscopy to complexes of Ag(+) and Ac-Tyr-NHMe (a model for GYG) which is a portion of the selectivity filter in the K(+) channel to consider the question of permeation. With support from quantum chemical calculations, we have determined the stable conformations of the complex. The conformations strongly suggest that Ag(+) would not readily permeate the K(+) channel. The mechanism of the unexpected enhancement by the inhibitor is discussed.