Silver Ion Triggers Ca 2+ Release from Intracellular Store Sites in Saponin-Treated HL-60 Cells

Abstract

Abstract

We examined the effect of silver ion on Ca²⁺ mobilization from intracellular stores in permeabilized HL-60 cells using a filtration method and ⁴⁵Ca²⁺. In HL-60 cells preloaded with Ca²⁺ in the presence of ATP, micromolar concentrations of AgNO₃ elicited marked Ca²⁺ release within 1 min. The AgNO₃-induced Ca²⁺ release was not affected by the free Ca²⁺ concentration in the medium. Equivalent concentrations of AgNO₃ inhibited energy-dependent Ca²⁺ uptake as well as oxalate-supported Ca²⁺ uptake. In passive Ca²⁺ release experiments when ATP was completely depleted in the solution, AgNO₃ also triggered Ca²⁺ release. Sulfhydryl protecting agents such as 2-mercaptoethanol, dithiothreitol, and glutathione (reduced form) blocked the AgNO₃-induced Ca²⁺ release. From these results, we conclude that the apparent Ca²⁺ release induced by AgNO₃ is mainly due to inhibition of the Ca²⁺ pump with increased permeability for Ca²⁺ and partly due to a direct effect on the Ca²⁺ release channel, probably by modification of sulfhydryl groups on these proteins.