Small Molecule Channels Harness Membrane Potential to Concentrate Potassium in trk1Δtrk2Δ Yeast

Abstract

Many protein ion channels harness membrane potential to move ions in opposition to their chemical gradient. Deficiencies of such proteins cause several human diseases, including cystic fibrosis, Bartter Syndrome Type II, and proximal renal tubular acidosis. Using yeast as a readily manipulated eukaryotic model system, we asked whether, in the context of a deficiency of such protein ion channel function in vivo, small molecule channels could similarly harness membrane potential to concentrate ions. In yeast, Trk potassium transporters use membrane potential to move potassium ions from a compartment of relatively low concentration outside cells ([~]15mM) to one of >10 times higher concentration inside (150-500mM). trk1{Delta}trk2{Delta} yeast are missing these potassium transporters and thus cannot concentrate potassium or grow in standard media. Here we show that potassium permeable, but not potassium selective, small molecule ion channels formed by the natural product amphotericin B can harness membrane potential to concentrate potassium in trk1{Delta}trk2{Delta} cells and thereby restore growth. This finding expands the list of potential human channelopathies that might be addressed by a molecular prosthetics approach.