Changes of the compositional asymmetry of phospholipids associated to the increment in the membrane surface potential.

The contribution of phosphatidylinositol (PI) and phosphatidylserine (PS) to the outer negative membrane surface potential was studied in normal, PS-rich and PI-rich yeast cells. Under carefully defined conditions; PS and PE were quantified by using the non-penetrating chemical probe trinitrobenzenesulfonic acid (TNBS) and the PI by degradation with a specific phospholipase C. An asymmetric distribution of phospholipids in the plasma membrane with more PS (80-90%), PI (70-85%) and PE (70-85%) in the inner leaflet was found. When compared to normal cells there were 3-times more PI and 2-times more PS in the outer leaflet of the PI-rich and PS-rich cells. These values are consistent with the two-times increased surface potential in these cells. Interestingly, the contribution of PI was around twice the contribution of PS to the surface potential in the cells studied. When compared to normal cells there was a two-times increased accessibility of PS to TNBS in the PI-rich cells and the accessibility of PI to phospholipase C was also increased two-times in the PS-rich cells, while the proportion of derivatized PE was similar in all cells. Taking into account that the amount of PI is similar in normal cells and PS-rich cells and the amount of PS is similar in PI-rich cells and normal cells, a charge driven transbilayer transport of acidic phospholipids can be proposed.