Multiple Inositol 1,4,5-Trisphosphate Receptor Isoforms Are Present in Platelets

Abstract

Platelets are activated by an increase in cytosolic Ca2+, and a portion of this increase is derived from inositol 1,4,5-trisphosphate (InsP3)-mediated Ca2+release from internal stores via the InsP3receptor. There is some uncertainty concerning the localization of the InsP3receptor within platelets, and experiments were designed to help resolve this question. [3H]InsP3binding to unphosphorylated and phosphorylated platelet internal membranes revealed both low and high affinity InsP3binding sites, indicating the presence of more than one isoform of InsP3receptor within the internal membranes. Phosphorylation did not significantly affect InsP3binding. In contrast, a single class of high affinity sites was observed in plasma membranes indicating only one type of InsP3receptor. Western blotting of platelet internal and plasma membranes with antibodies against the three major InsP3receptor isoforms revealed that the internal membranes contain both type 1 and type 2 InsP3receptors while the plasma membrane contains only InsP3receptor type 2.