Department of Integrated Chinese and Western Medicine, First Hospital, Peking University, Beijing, China.
Am J Chin Med. 2010;38(1):113-25. doi: 10.1142/S0192415X10007701.
Overload of intracellular calcium caused by amyloid-beta peptide has been implicated in the pathogenesis of neuronal damage in Alzheimer's disease. Voltage-gated calcium channels (VGCCs) provide one of the major sources of Ca(2+) entry into cells. Here, we investigated whether icariin had effect on the changes of calcium currents induced by Abeta(25-35) in hippocampal pyramidal neurons. Using whole-cell patch-clamp, we showed that Abeta(25-35) enhanced the inward Ba(2+) and Ca(2+) currents. The currents were partially inhibited by Ni(2+) and completely suppressed by Cd(2+), indicating that Abeta(25-35) disrupts intracellular calcium homeostasis via the modulation of both L- and T-type channels. Furthermore, icariin nearly complete suppressed the abnormal inward calcium currents induced by Abeta(25-35) in a dose-dependant manner. Our findings suggest that the potential neuroprotective effect of icariin on Abeta(25-35)-induced neurotoxicity via the balance intracelluar calcium homeostasis.
淀粉样肽β引起的细胞内钙超载被认为与阿尔茨海默病神经元损伤的发病机制有关。电压门控钙通道(VGCCs)提供了细胞内 Ca(2+)进入的主要来源之一。在这里,我们研究了淫羊藿苷是否对 Abeta(25-35)诱导的海马锥体神经元钙电流变化有影响。使用全细胞膜片钳技术,我们发现 Abeta(25-35)增强了内向的 Ba(2+)和 Ca(2+)电流。该电流部分被 Ni(2+)抑制,完全被 Cd(2+)抑制,表明 Abeta(25-35)通过调节 L 和 T 型通道破坏了细胞内钙稳态。此外,淫羊藿苷以剂量依赖的方式几乎完全抑制了 Abeta(25-35)诱导的异常内向钙电流。我们的研究结果表明,淫羊藿苷通过平衡细胞内钙稳态对 Abeta(25-35)诱导的神经毒性具有潜在的神经保护作用。