The effects of ruthenium red (RR) on inositol 1,4,5-trisphosphate (InsP3)-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 InsP3 (100 μM) increased intracellular Ca2+ concentration ([Ca2+]i) and activated the Ca2+-dependent K+ current. Administering InsP3 together with RR (100-500 μM) inhibited InsP3-induced responses (both Ca2+ and current responses) in a dose-dependent fashion. Pretreatment of megakaryocytes with extracellular RR (50 μM) also inhibited InsP3-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 InsP3-induced responses. Taken together, these results suggest that the site of the inhibitory action of RR is at the InsP3 receptor, or its closely associated proteins. In addition, we have shown that RR is a useful pharmacological tool with which to examine the InsP3-mediated responses of megakaryocytes.
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