Changes in erythrocyte permeability due to palytoxin as compared to amphotericin B

Abstract

Palytoxin causes within minutes a temperature-dependent K + loss from human and rat erythrocytes which is followed within hours by haemolysis. It decreases the osmotic resistance in a concentration-dependent manner, so that osmotic influences are negligible for K + release but considerable in haemolysis. External K + inhibits the haemoglobin release and Rb + inhibits the release of K + and haemoglobin. Ca 2+ (over 20 μM) and borate (over 5 μM) enhance the loss of K + and haemoglobin. With both Ca 2+ and borate present, the efficacy of palytoxin is raised about 10 000-fold. Under these conditions, about 15 palytoxin molecules per human cell trigger a 50% K + loss over a wide range of cell concentrations. The palytoxin effect is reversible. After depletion from K + by low concentrations of palytoxin, human cells can be refilled with K + and resealed. The pores formed by palytoxin are small. They allow the entrance of Na + and choline, whereas inositol is largely excluded and Ca 2+, as well as sucrose and inulin, are completely excluded. Amphotericin B resembles palytoxin in its ability to cause a considerable prelytic K + loss and to form small pores. However, it is about 1 000-times weaker than palytoxin, is not inhibited by K + or Rb +, is not activated by Ca 2+ or borate, and has a negative temperature dependence. Thus palytoxin represents a novel type of cytolysin.