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

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...

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Bibliographic Details
Published in:ACS chemical biology 2020-06, Vol.15 (6), p.1575-1580
Main Authors: Hou, Jennifer, Daniels, Page N, Burke, Martin D
Format: Article
Language:English
Subjects:
Cation Transport Proteins - genetics
Cation Transport Proteins - metabolism
Dose-Response Relationship, Drug
Humans
Membrane Potentials
Potassium Channels - drug effects
Potassium Channels - metabolism
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Small Molecule Libraries - pharmacology
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Summary: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 , 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); trk1Δtrk2Δ are 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 trk1Δtrk2Δ growth. This finding expands the list of potential human channelopathies that might be addressed by a molecular prosthetics approach.
ISSN:1554-8929
1554-8937
DOI:10.1021/acschembio.0c00180