Peña Antonio, Calahorra Martha, Michel Bertha, Ramírez Jorge, Sánchez Norma Silvia
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., Mexico.
FEMS Yeast Res. 2009 Sep;9(6):832-48. doi: 10.1111/j.1567-1364.2009.00538.x. Epub 2009 Jun 11.
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 Deltatok1 and Deltanha1 mutations resulted in a smaller effect of amiodarone, and Deltatrk1 and Deltatrk2 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.
在本研究中，极低浓度的胺碘酮可导致明显的钾离子外流。浓度增加时还会引起质子内流，导致细胞外pH升高和细胞内pH降低。钾离子外流导致质膜电位差增大，这是钙离子和氢离子进入、阴离子外流以及随后因细胞质钙离子浓度升高和细胞内pH降低而产生变化的原因。Deltatok1和Deltanha1突变导致胺碘酮的作用较小，而Deltatrk1和Deltatrk2显示质膜电位升高幅度更大。更高浓度的胺碘酮还会完全抑制呼吸作用，对解偶联剂不敏感，并部分抑制发酵作用。这种现象似乎在一系列能够通过降低细胞膜表面负电荷、使该阳离子直接作用于单价阳离子载体以及/或者使膜结构紊乱并改变载体功能来导致钾离子外流的阳离子分子中普遍存在，可能不仅在酵母中如此。
