Satrústegui J, Villalba M, Pereira R, Bogónez E, Martínez-Serrano A
Department of Molecular Biology, Center of Molecular Biology "Severo Ochoa" Autonomous University of Madrid, Spain.
Life Sci. 1996;59(5-6):429-34. doi: 10.1016/0024-3205(96)00322-0.
Synaptosomal [Ca2+]i levels increase during aging, particularly in the old rat hippocampus, both under basal conditions and after high K depolarization. This is probably the result of age-dependent modifications in calcium buffering and extrusion systems rather than due to increased calcium influx, since calcium uptake through synaptosomal voltage gated calcium channels decreases in old animals. The calcium binding capacity of the cytosolic compartment (i.e, that excluded from mitochondria and endoplasmic reticulum) of synaptosomes was markedly reduced in old rats. Calcium compartmentation in synaptosomal mitochondria, is also reduced during aging, and this is associated with a decrease in activity of the mitochondrial calcium uniporter. Taken together, these modifications point towards a clear deterioration of the cell calcium homeostatic mechanisms towards increased [Ca2+]i in old age, specially under conditions of high calcium loads, a situation that may exacerbate neuronal vulnerability to excitotoxicity.
在衰老过程中，无论是在基础条件下还是在高钾去极化后，突触体[Ca2+]i水平都会升高，尤其是在老年大鼠海马体中。这可能是钙缓冲和外排系统随年龄变化的结果，而不是由于钙内流增加，因为老年动物通过突触体电压门控钙通道的钙摄取减少。老年大鼠突触体的胞质区室（即排除线粒体和内质网的部分）的钙结合能力明显降低。突触体线粒体中的钙分隔在衰老过程中也会减少，这与线粒体钙单向转运体活性的降低有关。综上所述，这些变化表明，细胞钙稳态机制在老年时明显恶化，导致[Ca2+]i升高，特别是在高钙负荷条件下，这种情况可能会加剧神经元对兴奋性毒性的易感性。
