title: Charge selectivity of the designed uncharged peptide ion channel Ac-(LSSLLSL)3-CONH2.
abstract: Charge selectivity in ion channel proteins is not fully understood. We have studied charge selectivity in a simple model system without charged groups, in which an amphiphilic helical peptide, Ac-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, forms ion channels across an uncharged phospholipid membrane. We find these channels to conduct both K+ and Cl-, with a permeability ratio (based on reversal potentials) that depends on the direction of the KCl concentration gradient across the membrane. The channel shows high selectivity for K+ when [KCl] is lowered on the side of the membrane that is held at a positive potential (the putative C-terminal side), but only modest K+ selectivity when [KCl] is lowered on the opposite side (the putative N-terminal side). Neither a simple Nernst-Planck electrodiffusion model including screening of the helix dipole potential, nor a multi-ion, state transition model allowing simultaneous cation and anion occupancy of the channel can satisfactorily fit the current-voltage curves over the full range of experimental conditions. However, the C-side/N-side dilution asymmetry in reversal potentials can be simulated with either type of model.
authors.affiliation: DuPont Merck Pharmaceutical Co., Wilmington, Delaware 19880, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Kienker
authors.forename: J D
authors.initials: JD
authors.lastname: Lear
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions; D055592:Biophysical Phenomena; D001703:Biophysics; D002412:Cations; D004058:Diffusion; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011189:Potassium Chloride / Q000737:chemistry; D012996:Solutions
chemical_list: D000838:Anions; D002412:Cations; D007473:Ion Channels; D008051:Lipid Bilayers; D010455:Peptides; D012996:Solutions; D011189:Potassium Chloride