Quantal calcium release by purified reconstituted inositol 1,4,5-trisphosphate receptors

RELEASE of intracellular Ca²⁺ by inositol 1,4,5-trisphosphate (InsP3) occurs through specific receptor proteins1 which are ligand-activated Ca²⁺ channels . Changes in intracellular Ca²⁺ regulate many cellular functions3. This Ca²⁺ release is a discontinuous quantal process in which successive increments of InsP3 transiently release precise amounts of Ca²⁺ (refs 4-6). Possible explanations of quantal Ca²⁺ release have included rapid degradation of InsP3, reciprocity of Ca²⁺ release and sequestration, desensitization of InsP3 receptors7, or actions of InsP3 on discrete compartments of Ca²⁺ with variable sensitivity to InsP3 (ref. 4). We successfully reconstituted InsP3-induced Ca²⁺ flux in vesicles containing only purified InsP3 receptor protein². The reconstituted vesicles retain the regulatory features of the InsP3 receptor, including phosphory-lation sites⁸ and modulation of Ca²⁺ release by adenine nucleo-tides⁹. Using these reconstituted vesicles, we show here that quantal flux of Ca²⁺ elicited by InsP3 is a fundamental property of its receptor.