The mechanism of vanadium action on selective K+-permeability in human erythrocytes

Low concentrations of chelating agents such as EDTA prevent the air oxidation of vanadyl (VO²⁺, +4 oxidation state) to vanadate (VO₃^?, +5 oxidation state). Under these conditions, the ionophore A23187 mediates the rapid entry of vanadyl into human erythrocytes. In the presence of A23187, vanadyl at concentrations in excess of EDTA gives rise to a dramatic increase in K⁺ permeability, which is very similar to the Gardos Ca²⁺-induced K⁺ permeability increase with respect to ion selectivity, response to inhibitors, effects of pH, and stimulation by external K⁺. In ultrapure media with very low Ca²⁺, however, vanadyl has no effect on K⁺ permeability. These experiments suggest that Ca²⁺ is displaced from EDTA by vanadyl and then enters the cell via A23187 where it triggers the increase in K⁺ permeability. This hypothesis is confirmed by experiments demonstrating that vanadyl does displace Ca²⁺ from EDTA. Vanadate, an inhibitor of Ca²⁺-ATPase, causes a selective increase in K⁺ permeability in metabolically depleted cells, but the increase is abolished by low concentrations of EDTA, indicating that this effect is also due to entry of extracellular Ca²⁺. Earlier observations of effects of vanadyl and vanadate on erythrocyte K⁺ permeability can thus be explained on the basis of inhibition of the Ca²⁺ pump by vanadium, leading to an increase in intracellular Ca²⁺ concentration.