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 pHo = 5.5: I− ≈ Br− > Cl− > SCN− > NO 3 − , and at pHo 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 pHo = 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.