Anion currents in yeast K ⁺ transporters (TRK) characterize a structural homologue of ligand-gated ion channels

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.