The Effects Of Unaggregated Amyloid β Protein (25-35) On Potassium Channel Currents In Rat Hippocampal CA3 Pyramidal Neurons

[Objective]Alzheimer's disease (AD) is a progressive neurodegenerative condition affecting the memory and cognitive abilities. It is widely believed that the cellular actions of β Protein (Aβ) are responsible for the neurodegeneration observed in AD. Aggregated Aβ has been shown to have clear neurotoxic effects, but the effects of unaggregated Aβ is unclear yet.The effects of unaggregated Aβ on voltage-gated K+ channel were studied using the whole-cell patch clamp technique. To explore the mechanism of unaggregated Aβ in AD at ionic channel level. [Methods]Rat hippocampal CA3 pyramidal neurons were acutely dissociated. Using patch clamp technique, we recorded the total currents, the inward currents, the outward currents, the transient outward potassium current and delayed rectifier potassium current in Rat hippocampal CA3 pyramidal neurons. We analyzed the timing characteristic, I-V curves and dynamic characteristics of I_A and Ik-Using acute extracellular exposure, we recorded the relative currents after putting unaggregated AP25-35. All results were analyzed in relative computer software. [Results]1. Acutely dissociated rat hippocampal CA3 pyramidal neurons can liveand remain natural physiological function for 4~6h. They satisfied the need of patch clamp experiment.2. The electricity-physiological characteristics of rat hippocampal CA3 pyramidal neuronsThe total currents we recorded include two components- inward currents and outward currents. At first , it is mainly inward currents, which were fast activated and fast inactivated. Then outward currents were activated.(2) Activated potential of Ia is -30mV. Its range reduced continually, and reached steady state at 5min.(3) Activated potential of Ik is -20mV. Its range reduced continually, and reached steady state at 7min.3. The Effects of Unaggregated Aβ25.35 on IA in rat hippocampal CA3 pyramidal neurons(1) At first time, Aβ25.35 induced Ia continually, and reached steady state at 5min.(2) The effects of Aβ25-35 on IA in a concentration -dependent manner. The effects were enhanced with concentration increasing. lumol/L Aβ25-35 induced IA 44.27±8.93% and 5umol/L AP25-35 induced IA 62.20±10.83%.(3) From I-V curve, we found AP25-35 blocking effects were partly voltage-dependent, but IA activated potential was not change.(4) AP25.35 influence the dynamic characteristics of IA: Its activation curve and inactivation curve were both moving to left in a concentration-dependent manner.4. The Effects of Unaggregated AP25-35 on Ik in rat hippocampal CA3 pyramidal neurons(1) At first time, AP25-35 induced Ik continually, and reached steady state...