bkβ4通道动力学和生理功能分析word格式论文.docxVIP

优秀毕业论文 精品参考文献资料 Abstract Large conductance voltage-dependent Ca2+-activated potassium (BK) channels, are abundantly distributed in excitable and unexcitable cells. BK channels are tetramer of Slo1 α subunits and auxiliary β subunits. They play a critical role in modulating many physiological activities, such as neurotransmitter release and endocrine secretion in neurons or endocrine cells, contraction in smooth muscle cells and even frequency tuning in hair cells. Usually, these modulations are always in part with different β subunits. Among the four tissue specific β subunits, β4 subunit has been found specifically distributed in the nervous system, particularly in the brain. The β4-knockout mice displayed nerve firing potential disorders and temporal lobe seizure. BK channels, when associated with β4 subunits, showed significant slow activation and deactivation kinetics. Moreover, the regulation of β4 subunits on Ca2+-sensitivity is relatively complex: decreased the calcium sensitivity at low calcium concentrations, but increased the calcium sensitivity at high calcium concentrations. Using electrophysiological techniques and computational simulation, we simulated a 10-state kinetic model for BK(β4) channel based on Monod-Wyman-Changeux (MWC) in 0 μM, 1 μM, 10 μM and 300 μM calcium solution. This model can well describe the BK channels’ G-V curves and activation (deactivation) time constant with parameters approximately response to the characteristics of the channel. And by action potential simulation in hippocampus neuron cell, this model can also exactly reflect the characteristics of BK(β4) channels, which significantly slow down the firing frequency of action potential. Our 10-state model can accurately describe kinetics characteristics of BK(β4) channels. These results provide a basis for simulation of action potential in hippocampus neuron cell in the brain, which lay a theoretical foundation for study of the mechanism of epilepsy seizures. Keywords: BK