Investigating Potassium Channels in Budding Yeast: A Genetic Sandbox

Like all species, the model eukaryote Saccharomyces cerevisiae, or Bakers' yeast, concentrates potassium in the cytosol as an electrogenic osmolyte and enzyme cofactor. Yeast are capable of robust growth on a wide variety of potassium concentrations, ranging from 10 µM to 2.5 M, due to the presence of a high-affinity potassium uptake system and a battery of cation exchange transporters. Genetic perturbation of either of these systems retards yeast growth on low or high potassium, respectively. However, these potassium-sensitized yeast are a powerful genetic tool, which has been leveraged for diverse studies. Notably, the potassium-sensitive cells can be transformed with plasmids encoding potassium channels from bacteria, plants, or mammals, and subsequent changes in growth rate have been found to correlate with the activity of the introduced potassium channel. Discoveries arising from the use of this assay over the past three decades have increased our understanding of the structure-function relationships of various potassium channels, the mechanisms underlying the regulation of potassium channel function and trafficking, and the chemical basis of potassium channel modulation. In this article, we provide an overview of the major genetic tools used to study potassium channels in S. cerevisiae, a survey of seminal studies utilizing these tools, and a prospective for the future use of this elegant genetic approach.