水杨酸钠对大鼠海马神经元电压门控性离子通道的影响

发布时间：2018-01-27 14:18

本文关键词： 水杨酸钠耳鸣海马神经元电压门控性离子通道全细胞膜片钳　出处：《河北医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：耳鸣是一种常见的听觉系统疾病，其特点是在无外部相应声源的情况下耳内出现的幽灵般的铃音或蜂鸣声，是一种主观的声音感觉。临床医生已经注意到了耳鸣和情绪状态之间的关系。近年来有研究发现边缘系统某些相关核团参与耳鸣的不良情绪形成，例如海马。水杨酸钠过量能够引起耳鸣，是研究耳鸣发生机制的重要的工具药。本课题利用全细胞膜片钳技术研究水杨酸钠对大鼠海马部位神经元上的电压门控性钾、钠、钙离子通道的影响，探讨海马神经元上电压门控性离子通道与耳鸣的不良情绪之间的关系。一共分为三部分：一、水杨酸钠对海马神经元电压门控性钾离子通道的影响目的和方法：本实验利用脑片膜片钳技术观察水杨酸钠对大鼠海马神经元瞬时外向钾通道和延迟整流钾通道的影响。观察给予1mM水杨酸钠前后，IK(A)和IK(DR)的I-V曲线、稳态激活曲线、稳态失活曲线的变化情况。结果：水杨酸钠对IK(A)和IK(DR)均有抑制作用，且具有浓度依赖性。水杨酸钠对IK(A)的稳态激活动力学和稳态失活动力学没有影响。但是对IK(DR)的稳态激活动力学和稳态失活动力学均有影响。1mM的水杨酸钠使IK(DR)的稳态激活曲线向超极化方向移动大约12mV，稳态失活曲线向超极化方向移动大约19mV。结论：水杨酸钠通过对海马部位神经元上的瞬时外向钾通道和延迟整流钾通道的抑制作用，使动作电位的持续时间延长，增强神经递质的释放，加快神经元的重复放电节律，提高神经元的兴奋性。二、水杨酸钠对海马神经元电压门控性钠离子通道的影响目的和方法：本实验我们利用脑片膜片钳技术观察水杨酸钠对大鼠海马神经元电压门控性钠通道电生理学特征的影响。观察了给予1mM水杨酸钠前后，INA的I-V曲线、稳态激活曲线、稳态失活曲线的变化情况。结果：水杨酸钠对INA有抑制作用，且具有浓度依赖性。水杨酸钠对INA的稳态激活曲线有影响，使其稳态激活曲线向超极化方向移动10mV左右，但是对其的稳态失活曲线没有影响。结论：水杨酸钠通过对海马部位神经元上的电压门控性钠离子通道的抑制作用，降低动作电位产生的阈值，提高神经元的兴奋性，，使神经元处于过度兴奋状态，促进神经元的重复放电和神经递质的释放。三、水杨酸钠对海马神经元电压门控性钙离子通道的影响目的和方法：本实验利用脑片膜片钳技术观察水杨酸钠对大鼠海马神经元电压门控性钙离子通道电生理学特性的影响。观察了给予1mM水杨酸钠前后，ICa的I-V曲线、稳态激活曲线、稳态失活曲线的变化情况。结果:水杨酸钠对ICa有抑制作用而且具有浓度依赖性。水杨酸钠使ICa的稳态激活曲线向超极化方向移动大约9mV左右，但是对其稳态失活动力学没有显著影响。结论：水杨酸钠通过对海马部位神经元上的电压门控性钙通道的抑制作用，导致海马神经元的神经递质的释放减少，这可能是抑制性神经递质减少的主要原因。而抑制性神经递质减少后会导致神经元过度兴奋。总结：水杨酸钠对海马部位神经元IK(DR)的抑制作用（IC50为1.43mM）其对海马神经元ICa的抑制作用（IC50为1.64mM）其对海马神经元INa的抑制作用（IC50为2.07）其对海马神经元IK(A)的抑制作用（IC50为2.18mM）。水杨酸钠改变IK(DR)的稳态激活曲线和稳态失活曲线，使其向超级化方向移动；同时水杨酸钠改变INa和ICa的稳态激活曲线，使其向超级化方向移动；但是水杨酸钠对IK(A)的稳态激活曲线和稳态失活曲线均没有影响。
[Abstract]:tinnitus is a kind of common auditory system disease , which is characterized by the presence of a ghostly ringing tone or beep in the ear without external corresponding sound source . The clinical doctor has noticed the relationship between tinnitus and emotional state . In recent years , it has been found that some related nuclei of the limbic system are involved in the formation of bad mood of tinnitus , such as the excessive amount of sodium salicylate can cause tinnitus , and it is an important tool for studying the mechanism of tinnitus . Effect of Sodium Salicylate on Voltage - gated Potassium Ion Channels in Hippocampus Neurons Objective : To observe the effect of sodium salicylate on transient outward potassium channel and delayed rectifier potassium channel in rat hippocampal neurons by using the technique of brain slice patch clamp . The changes of I - V curve , steady state activation curve and steady - state inactivation curve of IK ( A ) and IK ( DR ) were observed before and after administration of 1 mM sodium salicylate . RESULTS : Sodium salicylate inhibited IK ( A ) and IK ( DR ) and had a concentration - dependent effect . Sodium salicylate had no effect on the steady - state activation kinetics and steady - state loss of motion of IK ( A ) . However , the steady - state activation kinetics of IK ( DR ) and steady - state loss of activity were affected . 1 mM sodium salicylate shifted the steady - state activation curve of IK ( DR ) to a hyperpolarization direction of about 12 mV , and the steady - state inactivation curve shifted about 19 mV to the hyperpolarization direction . Conclusion : Sodium salicylate can prolong the duration of action potential , enhance the release of neurotransmitters , accelerate the repetitive discharge rhythm of neurons , and improve the excitatory properties of neurons by inhibiting the transient outward potassium channels and delayed rectifier potassium channels on the neurons of the hippocampus . Effect of Sodium Salicylate on Voltage - gated Sodium Ion Channels in Hippocampus Neurons Objective and Methods : We observed the effect of sodium salicylate on electrophysiological characteristics of voltage - gated sodium channel in rat hippocampal neurons by using the technique of slice patch clamp . The changes of I - V curve , steady - state activation curve and steady - state inactivation curve of INA were observed before and after administration of 1 mM sodium salicylate . RESULTS : Sodium salicylate inhibited INA ' s steady - state activation curve and its steady - state activation curve shifted to the hyperpolarization direction by about 10 mV , but it had no effect on the steady - state inactivation curve . Conclusion : The inhibitory effect of sodium salicylate on the voltage - gated sodium ion channel on the neurons in the hippocampus is reduced , the threshold of action potential is decreased , the neurons are excited , the neurons are excited , the repetitive discharge of neurons and the release of neurotransmitters are promoted . Effect of sodium salicylate on voltage - gated calcium channel in hippocampus neurons Objective and Methods : To observe the effect of sodium salicylate on the electrophysiological properties of voltage - gated calcium channel in rat hippocampal neurons by using the technique of slice patch clamp . The changes of I - V curve , steady - state activation curve and steady - state inactivation curve of ICa before and after administration of 1 mM sodium salicylate were observed . RESULTS : Sodium salicylate inhibited ICa and had a concentration - dependent effect . The steady - state activation curve of ICa moved about 9 mV to the hyperpolarization direction , but there was no significant effect on its steady state loss mechanics . Conclusion : The inhibitory effect of sodium salicylate on the voltage - gated calcium channel in the hippocampal neurons leads to a decrease in the neurotransmitter release in the hippocampus neurons , which may be the main reason for the decrease of inhibitory neurotransmitter . The inhibitory effect of sodium salicylate ( IC50 of 1.43mM ) on the neurons of hippocampus was inhibited ( IC50 = 2.07 ) . The inhibitory effect of sodium salicylate on the neurons of hippocampus ( IC50 of 2.07 ) was inhibited ( IC50 = 2.18mM ) . The steady - state activation curve and steady - state inactivation curve of IK ( DR ) were changed to move towards the super - direction ; however , sodium salicylate did not influence the steady - state activation curve and the steady - state inactivation curve of IK ( A ) .

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R764

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