Regulation of Inositol 1,4,5-Trisphosphate-Induced Calcium Release by Inositol 1,4,5-Trisphosphate and Calcium in Human Platelets

Abstract

Inositol 1,4,5-trisphosphate (IP₃)-induced release of Ca²⁺, its regulation by IP₃ and Ca²⁺, and the metabolism of IP₃ was analyzed in saponin-permeabilized human platelets. At 37°C successive sub-maximal aliquots of IP₃ induce a biphasic release of part of the IP₃-sensitive Ca²⁺ pool each time. Although the IP₃-induced Ca²⁺ flux rapidly ceases after addition of IP₃, the IP₃-sensitive Ca²⁺ stores regain their sensitivity shortly after stimulation with IP₃. Under these conditions IP₃ is rapidly hydrolyzed to inositol 1,4-bisphosphate which is unable to release Ca²⁺. The cooperativity of IP₃-induced Ca²⁺ release and the metabolism of IP₃ can account for both the rapid recovery of sensitivity of the IP₃-sensitive Ca²⁺ pool and the partial release induced by sub-maximal concentrations of IP₃. The data of the present study favour a steady state rather than an all-or-none mechanism of Ca²⁺ release.