Cd2+-induced damage to yeast plasma membrane and its alleviation by Zn2+: studies on Schizosaccharomyces pombe cells and reconstituted plasma membrane vesicles

In Schizosaccharomyces pombe, Cd2+ shares the same uphill uptake system with Zn2+. Both heavy metals inhibited growth, respiration, H+/glucose uptake, and glucose-induced proton extrusion, Cd2+ being a 10-15-fold stronger inhibitor. In contrast, both had a similar effect on the plasma membrane H+-ATPase, enhancing its affinity for ATP and reducing the rate of ATP splitting. Cd2+ caused protracted strong fluidization of the plasma membrane of energized cells, whereas deenergized cells, phosphatidylcholine liposomes, and plasma membrane fragments, either purified or incorporated into the liposomes, exhibited only a short initial fluidization. Zn2+, which caused only a marginal membrane fluidization, suppressed the fluidizing action of Cd2+. The fluidizing effect of both heavy metals on liposomes was reduced by the presence of plasma membrane fragments in the liposome membrane. At 50 &mgr;M, Cd2+ brought about loss K+ (18 K+/1 Cd2+) from energized, but not from deenergized cells since Cd2+ must first accumulate in the cells before causing a detectable effect. A simple membrane disruption by external Cd2+ is, therefore, unlikely to be the main mechanism of cadmium-induced potassium loss in intact cells. Zn2+ had virtually no effect below 1 mM concentration, and it again weakened the K+-releasing effect of Cd2+. Cd2+ caused a strong loss of K+ also from K+-containing liposomes, probably because of a direct interaction with liposome phospholipids. Incorporation of plasma membrane fragments into the liposomes reduced the K+ loss sixfold.