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 Ca2+ and H+, the efflux of anions and the subsequent changes resulting from the increased cytoplasmic Ca2+ concentration, as well as the decreased internal pH. The Delta tok1 and Delta nha1 mutations resulted in a smaller effect of amiodarone, and Delta trk1 and Delta trk2 showed a higher increase of the plasma membrane potential. Higher concentrations of amiodarone also produced full inhibition of respiration, insensitive to uncouplers and a partial inhibition of fermentation. This phenomenon appears to be common to a large series of cationic molecules that can produce the efflux of K+, through the reduction of the negative surface charge of the cell membrane, and the concentration of this cation directly available to the monovalent cation carriers, and/or producing a disorganization of the membrane and altering the functioning of the carriers, probably not only in yeast.