Regulation of inositol 1,4,5-trisphosphate-induced calcium release by inositol 1,4,5-trisphosphate and calcium in human platelets.

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 degrees 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.