Ferris C D, Cameron A M, Huganir R L, Snyder S H
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Nature. 1992 Mar 26;356(6367):350-2. doi: 10.1038/356350a0.
Release of intracellular Ca2+ by inositol 1,4,5-trisphosphate (InsP3) occurs through specific receptor proteins which are ligand-activated Ca2+ channels. Changes in intracellular Ca2+ regulate many cellular functions. 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 receptors, 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 protein. The reconstituted vesicles retain the regulatory features of the InsP3 receptor, including phosphorylation sites and modulation of Ca2+ release by adenine nucleotides. Using these reconstituted vesicles, we show here that quantal flux of Ca2+ elicited by InsP3 is a fundamental property of its receptor.
肌醇1,4,5-三磷酸（InsP3）引发的细胞内Ca2+释放是通过特定的受体蛋白实现的，这些蛋白是配体激活的Ca2+通道。细胞内Ca2+的变化调节着许多细胞功能。这种Ca2+释放是一个不连续的量子过程，其中InsP3的连续增量会瞬时释放精确量的Ca2+（参考文献4-6）。量子Ca2+释放的可能解释包括InsP3的快速降解、Ca2+释放与螯合的相互作用、InsP3受体的脱敏，或InsP3对Ca2+离散区室的作用，这些区室对InsP3具有不同的敏感性（参考文献4）。我们成功地在仅含有纯化的InsP3受体蛋白的囊泡中重建了InsP3诱导的Ca2+通量。重建的囊泡保留了InsP3受体的调节特性，包括磷酸化位点以及腺嘌呤核苷酸对Ca2+释放的调节。利用这些重建的囊泡，我们在此表明InsP3引发的Ca2+量子通量是其受体的基本特性。
