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

Jennifer Hou, Page N. Daniels, Martin D. Burke

Research output: Contribution to journalArticle

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, and proximal renal tubular acidosis. Using yeast as a eukaryotic model system, we asked whether, in the context of a protein ion channel deficiency in vivo, small molecule channels could similarly harness membrane potential to concentrate ions. Trk potassium transporters use membrane potential to move potassium from a relatively low concentration outside cells (-15 mM) to one of >10× higher inside (150-500 mM); trk1Î"trk2Δare unable to concentrate potassium or grow in standard media. Here we show that potassium-permeable, but not potassium-selective, small-molecule ion channels formed by amphotericin B can harness membrane potential to concentrate potassium and thereby restore trk1Î"trk2Δgrowth. This finding expands the list of potential human channelopathies that might be addressed by a molecular prosthetics approach.

Original languageEnglish (US)
Pages (from-to)1575-1580
Number of pages6
JournalACS chemical biology
Volume15
Issue number6
DOIs
StatePublished - Jun 19 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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