Smalla Karl-Heinz, Sahin Jale, Putzke Jörg, Tischmeyer Wolfgang, Gundelfinger Eckart D, Kreutz Michael R
Special Lab Molecular Biological Techniques, Leibniz-Institute for Neurobiology, Magdeburg, Germany.
Neurochem Res. 2009 Aug;34(8):1405-9. doi: 10.1007/s11064-009-9925-8. Epub 2009 Feb 18.
Caldendrin is a synaptic calcium sensor protein that is tightly associated with the postsynaptic density (PSD). Previous work has shown that the association of the protein with the synapse is highly dynamic and is increased in an activity-dependent manner. In the present study the caldendrin-association with the postsynaptic cytomatrix was analyzed in animal models of psychosis and drug abuse induced neurotoxicity. Subchronic administration of the N-methyl-D-aspartate (NMDA)-receptor antagonist ketamine, serving as a model of NMDA-receptor hypofunction and schizophrenia showed no significant effect on the PSD-levels of caldendrin, indicating that NMDA-receptor activity is not required to keep caldendrin at the synapse. However, administration of high doses of the serotonergic neurotoxin p-chloroamphetamine (PCA) lead to significant changes in the association of caldendrin with the PSD. These results underscore the dynamic association of caldendrin with the PSD and suggest a role of this synaptic calcium sensor in the PCA-induced serotonin syndrome.
钙调蛋白是一种与突触后致密物（PSD）紧密相关的突触钙传感器蛋白。先前的研究表明，该蛋白与突触的结合高度动态，并以活动依赖的方式增加。在本研究中，在精神病和药物滥用诱导的神经毒性动物模型中分析了钙调蛋白与突触后细胞基质的结合。作为NMDA受体功能低下和精神分裂症模型的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂氯胺酮的亚慢性给药对钙调蛋白的PSD水平没有显著影响，表明在突触处保持钙调蛋白不需要NMDA受体活性。然而，高剂量的血清素能神经毒素对氯苯丙胺（PCA）的给药导致钙调蛋白与PSD结合的显著变化。这些结果强调了钙调蛋白与PSD的动态结合，并表明这种突触钙传感器在PCA诱导的血清素综合征中起作用。
