title: Anion currents in yeast K+ transporters (TRK) characterize a structural homologue of ligand-gated ion channels.
abstract: Patch clamp studies of the potassium-transport proteins TRK1,2 in Saccharomyces cerevisiae have revealed large chloride efflux currents: at clamp voltages negative to -100 mV, and intracellular chloride concentrations >10 mM (J. Membr. Biol. 198:177, 2004). Stationary-state current-voltage analysis led to an in-series two-barrier model for chloride activation: the lower barrier (α) being 10-13 kcal/mol located ~30% into the membrane from the cytoplasmic surface; and the higher one (β) being 12-16 kcal/mol located at the outer surface. Measurements carried out with lyotrophic anions and osmoprotective solutes have now demonstrated the following new properties: (1) selectivity for highly permeant anions changes with extracellular pH; at pH(o)= 5.5: I(-)≈ Br(-) >Cl(-) >SCN(-) >NO (3)(-) , and at pH(o) 7.5: I(-)≈ Br(-) > SCN(-) > NO(3)(-) >Cl(-). (2) NO(2)(-) acts like "superchoride", possibly enhancing the channel's intrinsic permeability to Cl(-). (3) SCN(-) and NO(3)(-) block chloride permeability. (4) The order of selectivity for several slightly permeant anions (at pH(o)= 5.5 only) is formate>gluconate>acetate>>phosphate(-1). (5) All anion conductances are modulated (choked) by osmoprotective solutes. (6) The data and descriptive two-barrier model evoke a hypothetical structure (Biophys. J. 77:789, 1999) consisting of an intramembrane homotetramer of fungal TRK molecules, arrayed radially around a central cluster of four single helices (TM7) from each monomer. (7) That tetrameric cluster would resemble the hydrophobic core of (pentameric) ligand-gated ion channels, and would suggest voltage-modulated hydrophobic gating to underlie anion permeation.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. alberto.rivetta@yale.edu
authors.forename: Alberto
authors.initials: A
authors.lastname: Rivetta
authors.forename: Teruo
authors.initials: T
authors.lastname: Kuroda
authors.forename: Clifford
authors.initials: C
authors.lastname: Slayman
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology; D058446:Ligand-Gated Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism*; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D000838:Anions; D058446:Ligand-Gated Ion Channels; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D011188:Potassium