Inhibitory effects of ruthenium red on inositol 1,4,5-trisphosphate-induced responses in rat megakaryocytes

The effects of ruthenium red (RR) on inositol 1,4,5-trisphosphate (InsP(3))-induced responses were studied in rat bone marrow megakaryocytes with the patch-clamp whole-cell recording technique in combination with fura-2 microfluorometry. Internal application of InsP(3) (100 muM) increased intracellular Ca2+ concentration ([Ca2+](i)) and activated the Ca2+-dependent K+ current. Administering InsP(3) together with RR (100-500 muM) inhibited InsP(3)-induced responses (both Ca2+ and current responses) in a dose-dependent fashion. Pretreatment of megakaryocytes with extracellular RR (50 muM) also inhibited InsP(3)-induced responses. Intracellular and extracellular application of RR reduced ADP-induced increases in [Ca2+](i). In contrast, in isolated single pancreatic acinar cells, RR had no effect on InsP(3)-induced responses. Taken together, these results suggest that the site of the inhibitory action of RR is at the InsP(3) receptor, or its closely associated proteins. In addition, we have shown that RR is a useful pharmacological tool with which to examine the InsP(3)-mediated responses of megakaryocytes. (C) 2000 Elsevier Science Inc. All rights reserved.