Israël M, Meunier F M, Morel N, Lesbats B
J Neurochem. 1987 Sep;49(3):975-82. doi: 10.1111/j.1471-4159.1987.tb00989.x.
A "fatigue" of acetylcholine (ACh) release is described in cholinergic synaptosomes stimulated with the calcium ionophore A23187 or gramicidin. A small conditioning calcium entry, which did not trigger a large ACh release, led to a decrease of transmitter release elicited by a second large calcium influx. This fatigue was half-maximal at approximately 30 microM external calcium and developed in a few minutes. In contrast, activation of release by calcium was very rapid and was half-maximal at approximately 0.5 mM external calcium. Activation and desensitization of release could be attributed to the recently identified presynaptic membrane protein, the "mediatophore." Proteoliposomes equipped with purified mediatophore showed a calcium-dependent activation and "fatigue" of ACh release similar to that of synaptosomes. It was found that the ionophore A23187 rapidly equilibrated internal and external calcium concentrations in proteoliposomes. Thus, the external calcium concentration gave the internal concentration required for activation or desensitization of proteoliposomal ACh release. The mediatophore showed remarkable calcium binding properties (20 sites/molecule) with a KD of 25 microM. The physiological implications of desensitization on the organization of release sites are discussed.
在用钙离子载体A23187或短杆菌肽刺激的胆碱能突触体中，描述了乙酰胆碱（ACh）释放的“疲劳”现象。一个小的条件性钙内流，它不会引发大量的ACh释放，却导致了由第二次大量钙内流所引发的递质释放减少。这种疲劳在约30微摩尔的细胞外钙浓度时达到半数最大效应，且在几分钟内就会出现。相比之下，钙对释放的激活非常迅速，在约0.5毫摩尔的细胞外钙浓度时达到半数最大效应。释放的激活和脱敏可归因于最近鉴定出的突触前膜蛋白“介质载体”。配备有纯化介质载体的蛋白脂质体显示出与突触体类似的ACh释放的钙依赖性激活和“疲劳”。研究发现，离子载体A23187能迅速平衡蛋白脂质体内外的钙浓度。因此，细胞外钙浓度决定了蛋白脂质体ACh释放激活或脱敏所需的细胞内浓度。介质载体显示出显著的钙结合特性（20个位点/分子），解离常数为25微摩尔。文中讨论了脱敏对释放位点组织的生理学意义。
