| Previous studies have shown that amyloid beta-protein(A P ) can facilitate the opening of voltage- gated calcium channels(VGCC), leading to the increase of calcium inflow and overload of intracellular calcium which result in the damage and apoptosis of nerve cell. Therefore, A is involved in the pathogenesis of Alzheimer's disease(AD). The epidemiology studies have shown that estrogen replacement therapy can decrease the risk of AD significantly, improve the symptom of AD patients and postpone the progress of AD. Furthermore, many studies have indicated that estrogen can inhibit the toxic effect of A P by many ways. Other studies indicate that some carbohydrate and their derivatives have a neuroprotective effect and have a great potential to treat the neurodegenerative diseases. Our previous experiments have shown that administration of native estrogen-like medicine, effective contraction of Bak Foong Pills(BFP), and ocean acidic oligosaccharide HSH971 can prevent the neurotoxicity of A P 1.40 on rat adrenal medulla Pheochromocytoma cells(PC12 cells) effectively. To understand the mechanism of BFP and HSH971 induced neuroprotective effect, we studied the effect of BFP and HSH971 on A induced facilitation of VGCC. PC 12 cells were divided into 6 groups: control group, A 1-40-treated group, BFP-treated group, A 1-40 +BFP-treated group, HSH971 -treated group and A 1-40 +HSH971 -treated group. Whole-cell patch-clamp recordings were performed in the present study to investigate the effects of different treatment on VGCC currents. Current density obtained by current-amplitude/membrane capacitance was used as a marker of Ca2+ inflax. The results were as follows:1. The VGCC current density of the cells incubated with A 1-40l M for 6h was significantly increased compared with that of the control group. (P<0.01)2. The VGCC current density of the cells co-incubated with A 1-40l M and BFP100 g/ml was significantly reduced compared with that of A -treated group.(P<0.01)3. Co-incubated with A 1-40 1MM and HSH971 400 g/ml for 6h, the VGCC current density was also significantly reduced compared with that of A -treated group. (P<0.01)4. There was no significant difference of the VGCC current density between control group and BFP or HSH971 treated group. (P>0.05)In summary, the present results suggested that A 1.40 can increase the VGCC currents of PC12 cell, which results in the increased Ca2+ influx leading to disruption of calcium homeostasis and activation of various biological effects causing cell damage. Furthermore, incubation with BFP can inhibit the effect of A P 1.40 on the VGCC currents obviously so that reduce the calcium influx, avoiding Ca2+ overload to provide neuroprotection. The results provides some experimental evidence for the prevention and treatment of Alzheimer's disease.The present studies have also shown that HSH971 can reduce A 1-40 induced neurotoxicity of PC12 cells via inhibiting the effect of A 1-40 on the VGCC currents, which provide preliminary evidence for its neuroprotive effects.
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