TY - JOUR
T1 - Small Molecule Channels Harness Membrane Potential to Concentrate Potassium in trk1Δtrk2Δ Yeast
AU - Hou, Jennifer
AU - Daniels, Page N.
AU - Burke, Martin D.
N1 - We are grateful to C. Grosman for thoughtful review of this manuscript, J. Ariño for the gift of the isogenic BY4741(WT) and BYT12(trk1Δtrk2Δ) Saccharomyces cerevisiae strains, K. Subedi, E. Eves, and C. Lu for their assistance with inductively coupled plasma-mass spectrometry analysis, which was performed at The UIUC Microanalysis Laboratory, and B. Pilas for her assistance with the flow cytometry protocol and analysis, which was performed at The Roy J. Carver Biotechnology Center at UIUC. We thank The National Institutes of Health (GM118185), and Howard Hughes Medical Institutes (HHMI) for funding support. P.N.D is an NIH Predoctoral Research Fellow (T32 GM070421). J.H. was supported partially by a UIUC Medical Scholars Program Fellowship.
PY - 2020/6/19
Y1 - 2020/6/19
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85086747657
UR - https://www.scopus.com/pages/publications/85086747657#tab=citedBy
U2 - 10.1021/acschembio.0c00180
DO - 10.1021/acschembio.0c00180
M3 - Article
C2 - 32427463
AN - SCOPUS:85086747657
SN - 1554-8929
VL - 15
SP - 1575
EP - 1580
JO - ACS chemical biology
JF - ACS chemical biology
IS - 6
ER -