| Part I The role of voltage -gated potassium channels on Amyloid-β peptide25-35 induced apoptosis and necrosis in the cultured rat hippocampal neuronsSenile plaques, a hallmark of AD brain pathology, contain 39-to 43-residue Amyloid β peptides. In vitro and in vivo experiments have shown that Aβ is toxic to many cells types. Aβ induced neuronal apoptosis played a important role in AD pathogenesis. To further elucidate the role of voltage-gated potassium channels in Amyloid- β peptide induced apoptosis and necrosis, we investigated the effect of chronic exposure to A β 25-35 on transient outward (IA), delayed rectifier(IK) current, Kv channel subtypes mRNA expression and Kv2.1 protein expression by using MTT assay, Hochest33342 fluorescent dying assay, whole cell patch clamping , RT-PCR and Western blot in the cultured rat hippocampal neurons. Our results showed that (1)MTT assay and Hochest 33342 fluorescent dying showed that A β 25-35 induced neuronal apoptosis and necrosis significantly. After exposure to 3 μ mol/L A β 25-35 for 48h, the cell viability was reduced by 26.2%±9.1%, and the percentage of apoptosis reached by35.8%±3.8%; (2)Cells exposure to 3 μmol/L A β 25-35 for 24 hr, the IK was increased by44.3% ± 5.4% (n=10,P<0.05) at the membrane potential of 40 mV , and the V1/2 of activation shifted from 4.5 ± 1.3mV to -6.9 ± 1.7 mV(n=10,p<0.05), When A β 25-35 was 10 μ mol/L, IK was increased by 69.8% ±4.1%(n=10,P<0.01) and shifted V1/2 of activation increased from4.5 ± 1.3mV to-9.9±2.1mV (n=10, p<0.01); A β 25-35 increased current was sensitive to 5mmol/L TEA. IA was not changed obviously after exposure to A β25-35 (P>0.05). (2) RT-PCR experiment showed that in the presence of A β25-353 μ mol/L for 24 h , the relative expression levels of Kv2.1 were significantly increased (n=3,P<0.05); the other subtypes including Kv1.5, Kv1.4, Kv4.2 and rSlo potassium channel subtypes mRNA expression were not changed obviously (n=3.P>0.05). The increase of Kv2.1 mRNA mainly...
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