CHARGE SELECTIVITY OF THE DESIGNED UNCHARGED PEPTIDE ION-CHANNEL AC-(LSSLLSL)(3)-CONH2

Charge selectivity in ion channel proteins is not fully understood. We have studied charge selectivity in a simple model system without char ged groups, in which an amphiphilic helical peptide, Ac-(Leu-Ser-Ser-L eu-Leu-Ser-Leu)(3)-CONH2, forms ion channels across an uncharged phosp holipid membrane. We find these channels to conduct both K+ and Cl-, w ith a permeability ratio (based on reversal potentials) that depends o n the direction of the KCl concentration gradient across the membrane. The channel shows high selectivity for KC when [KCl] is lowered on th e side of the membrane that is held at a positive potential (the putat ive C-terminal side), but only modest K+ selectivity when [KCI] is low ered on the opposite side (the putative N-terminal side). Neither a si mple Nernst-Planck electrodiffusion model including screening of the h elix dipole potential, nor a multi-ion, state transition model allowin g simultaneous cation and anion occupancy of the channel can satisfact orily fit the current-voltage curves over the full range of experiment al conditions. However, the C-side/N-side dilution asymmetry in revers al potentials can be simulated with either type of model.