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大鼠海马CA1区锥体神经元IA和IK在出生后早期的变化

陈小佳, 谭涛, 刘迢迢, 田心^*

天津医科大学1生物医学工程学院；2基础医学研究中心神经工程实验室，天津 300070

摘要

大脑快速发育期(brain growth spurt, BGS)是神经元生长、突触连接的关键时期；电压门控性K+通道是维持细胞兴奋性和神经元间信息传递的关键通道。本文旨在探究BGS期内大鼠海马CA1区锥体神经元电压门控性K+通道电流及其通道动力学特性的变化，以期找出大鼠海马CA1区锥体神经元电压门控性K+通道发育的关键期。采用全细胞膜片钳技术，研究出生后0~4周大鼠海马CA1区脑片上的锥体神经元全细胞电压门控性K+通道电流及其通道动力学特性。结果显示：在测试电压为+90 mV下，以出生后0周为参照，出生后1~4周的瞬时外向K+通道电流(IA)的最大电流密度的增幅分别为(16.14 ± 0.51)%、(81.73 ± 10.71)%、(106.72 ± 5.29)%、(134.58 ± 8.81)% (n = 10, P < 0.05)；延迟整流K+通道电流(IK)的最大电流密度增幅分别为(16.75 ± 3.88)%、(134.01 ± 2.85)%、(180.56 ± 8.49)%、(194.5 ± 8.53)% (n = 10, P < 0.05)，显示K+通道电流密度于1~2周增幅最大；IA的激活曲线向左移，半数激活电压随周龄增加逐渐减小，分别为14.67 ± 0.75、13.46 ± 0.64、8.39 ± 0.87、4.60 ± 0.96、0.54 ± 0.92 (mV, n = 10, P < 0.05)；IK的激活曲线向左移，半数激活电压随周龄增加逐渐减小，分别为8.94 ± 0.85、6.65 ± 0.89、0.47 ± 1.15、−1.80 ± 0.89、−8.56 ± 1.08 (mV, n = 10, P < 0.05)。IA的失活曲线向左移，0周龄与1周龄之间的半数失活电压没有显著性差异，而出生后1~4周随周龄增加半数失活电压逐渐减小(P < 0.05)，分别为−45.68 ± 1.26、−46.81 ± 0.78、−48.64 ± 0.81、−51.96 ± 1.02、−58.31 ± 1.35 (mV, n = 10)。以上结果表明，随着鼠龄的增加，IA和IK电流密度逐渐增加，电压门控性K+通道半数激活、失活电压降低，尤其是出生后1周至2周变化明显，上述变化与海马神经元的逐渐发育成熟及其功能的完善有关。

关键词： 瞬时外向K+通道电流; 延迟整流K+通道电流; CA1区锥体神经元; 海马脑片

分类号：R749.94

[Changes of IA and IK from the pyramidal neurons at hippocampal CA1 during the early development of rats.] [Article in Chinese]

CHEN Xiao-jia, TAN Tao, LIU Tiao-Tiao, TIAN Xin^*

Department of Biomedical Engineering； Laboratory of Neural Engineering, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China

Abstract

Brain growth spurt (BGS) is the critical period of neuronal growth and synaptic connection. The voltage-gated K(+) channel is the key channel for maintenance of cell excitability and information transfer among neurons. The purpose of the present study is to investigate the critical period of voltage-gated K(+) channel development in hippocampal CA1 neurons during the BGS. Changes of voltage-gated K(+) currents in neurons from acutely isolated hippocampal CA1 brain slices of rats at different ages (0-4 weeks after birth) were recorded by the whole-cell patch-clamp technique. The depolarization voltage was set at +90 mV, and 0 week was set as the control group. The experimental results showed that, with increasing ages (1-4 weeks), the maximum current densities of I(A) increased by (16.14 ± 0.51)%, (81.73 ± 10.71)%, (106.72 ± 5.29)%, (134.58 ± 8.81)% (n = 10, P < 0.05), and the maximum current densities of I(K) increased by (16.75 ± 3.88)%, (134.01 ± 2.85)%, (180.56 ± 8.49)%, (194.5 ± 8.53)% (n = 10, P < 0.05), respectively, compared with those in 0 week. During 0-4 weeks after birth, the activation kinetics of I(A) shifted to left, and the half activation voltages of I(A) were 14.67 ± 0.75, 13.46 ± 0.64, 8.39 ± 0.87, 4.60 ± 0.96, 0.54 ± 0.92 (mV, n = 10, P < 0.05), respectively; The activation kinetics of I(K) shifted to left and the half activation voltages of I(K) were 8.94 ± 0.85, 6.65 ± 0.89, 0.47 ± 1.15, -1.80 ± 0.89, -8.56 ± 1.08 (mV, n = 10, P < 0.05) respectively. The inactivation kinetics of I(A) also shifted to left, and the half inactivation voltages were -45.68 ± 1.26, -46.81 ± 0.78, -48.64 ± 0.81, -51.96 ± 1.02, -58.31 ± 1.35 (mV, n = 10) respectively at 0, 1, 2, 3 and 4 weeks after birth, which showed no significant changes between 0 and 1 week, but significant decreases during 1-4 weeks after birth (P < 0.05). These results indicate that the current densities of I(A) and I(K) increase and the kinetic characteristics of the voltage-gated K(+) channels change with increasing ages during 0-4 weeks after birth, and the differences are especially significant between the 1st week and the 2nd week after birth. These changes may be related to the maturation of hippocampal neurons and the progress of their functions.

Key words: transient outward K+ current; delayed rectifier K+ current; CA1 pyramidal neurons; hippocampal slice

收稿日期：2012-07-13　　录用日期：2012-10-23

通讯作者：田心　　E-mail: tianx@tijmu.edu.cn

引用本文：

陈小佳, 谭涛, 刘迢迢, 田心. 大鼠海马CA1区锥体神经元IA和IK在出生后早期的变化[J]. 生理学报 2013; 65 (2): 193-200.

CHEN Xiao-jia, TAN Tao, LIU Tiao-Tiao, TIAN Xin. [Changes of IA and IK from the pyramidal neurons at hippocampal CA1 during the early development of rats.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (2): 193-200 (in Chinese with English abstract).