Role Of Voltage-dependent Potassium Channels In Aβ_25-35-induced Neuronal Apoptosis And The Relevant Pharmacological Study

Aβ, a main component of senile plaques in AD, induces neuronal degeneration and apoptosis. The molecular toxic mechnisims involves factors such as formation of free radicals, destroying Ca²⁺ homestasis and aberrant inflammation. Recently it was reported that the increase of K⁺ efflux mediated by delayed rectifier potassium channel played an important role in Aβ-induced neuronal apoptosis. But not all experiments support the hypothesis that potassium channel activation promoted apoptosis. To clarify the importance of potassium channel in apoptosis, we observed the role of potassium channel in Aβ_25-35-induced apoptosis of hippocampal neurons.Donepezil and galantamine, the second generation of cholinesterase inhibitors (ChEIs), were used to the treatment of AD. It was reported that both of them blocked delayed rectifier potassium channels of rat hippocampal neurons in our previous study. However, the effects of donepezil and galantamine on subtypes of potassium channels remain unclear. Delayed rectifier potassium channels Kv1.5 and Kv2.1 are expressed at a high level in hippocampus. Therefore, the properties of cloned Kv1.5, Kv2.1 potassium channels and the effcts of donepezil, galantamine on them were investigated in this study.NBP, synthesized and developed as an anti-cerebral ischemic agent in our institute, potently inhibited neuronal apoptosis. Potassium channels play a vital role in cell apoptosis. Furthermore, it suggested that Kv1.5 and Kv2.1 channels might play a...