Effects of amiodarone on K+, internal pH and Ca2+ homeostasis in Saccharomyces cerevisiae.

In this study, amiodarone, at very low concentrations, produced a clear efflux of K(+). Increasing concentrations also produced an influx of protons, resulting in an increase of the external pH and a decrease of the internal pH. The K(+) efflux resulted in an increased plasma membrane potential difference, responsible for the entrance of Ca(2+) and H(+), the efflux of anions and the subsequent changes resulting from the increased cytoplasmic Ca(2+) concentration, as well as the decreased internal pH.

The yeast potassium transporter TRK2 is able to substitute for TRK1 in its biological function under low K and low pH conditions.

In S. cerevisiae, K+ transport relies principally on two structurally related membrane proteins, known as Trk1p and Trk2p. Direct involvement in cation movements has been demonstrated for Trk1p, which is a high-affinity K+ transporter.

The SUMO ubiquitin-protein isopeptide ligase family member Miz1/PIASxbeta /Siz2 is a transcriptional cofactor for TFII-I.

We have shown previously that a TFII-I-related protein, hMusTRD1/BEN, represses transcriptional activity of TFII-I. The repression by hMusTRD1/BEN was hypothesized to occur via a two-step competition mechanism involving a cytoplasmic shuttling factor and a nuclear cofactor required for transcriptional activation of TFII-I. Employing a two-hybrid approach with both yeast genomic and mouse cDNA libraries in parallel, we have identified the RING-like zinc finger containing Miz1/PIASxbeta/Siz2, which is a ubiquitin-protein isopeptide ligase in the SUMO pathway, as the potential nuclear cofactor that interacts with both TFII-I and hMusTRD1/BEN.