Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Ave., Urbana, Illinois 61801, United States.
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Ave., Urbana, Illinois 61801, United States.
ACS Chem Biol. 2020 Jun 19;15(6):1575-1580. doi: 10.1021/acschembio.0c00180. Epub 2020 Jun 3.
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.
许多蛋白质离子通道利用膜电位逆化学梯度转运离子。这些蛋白质的缺乏会导致多种人类疾病，包括囊性纤维化、巴特综合征和近端肾小管酸中毒。我们利用酵母作为真核生物模型系统，探究在蛋白质离子通道缺乏的情况下，小分子通道是否也能够利用膜电位来浓缩离子。Trk 钾转运体利用膜电位将钾从细胞外相对较低的浓度（约 15mM）转运到细胞内 10 倍以上的高浓度（150-500mM）；trk1Δtrk2Δ 无法浓缩钾或在标准培养基中生长。本文中，我们发现两性霉素 B 形成的钾通透性但非钾选择性小分子离子通道可以利用膜电位来浓缩钾，从而恢复 trk1Δtrk2Δ 的生长。这一发现扩展了潜在的人类通道病列表，这些疾病可能可以通过分子修复术的方法进行治疗。
