Zou Bende, Li Yan, Deng Ping, Xu Zao C
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 507, Indianapolis, IN 46202, USA.
Brain Res. 2005 Feb 1;1033(1):78-89. doi: 10.1016/j.brainres.2004.11.023.
CA1 pyramidal neurons in the hippocampus die 2-3 days following transient forebrain ischemia, whereas CA3 pyramidal neurons and granule cells in the dentate gyrus remain viable. Excitotoxicity is the major cause of ischemic cell death, and potassium currents play important roles in regulating the neuronal excitability. The present study compared the changes of potassium currents in acutely dissociated hippocampal neurons at different intervals after ischemia. In CA1 neurons, the amplitude of rapid inactivating potassium currents (I(A)) was significantly increased at 14 h and returned to control levels at 38 h after ischemia; the rising slope and decay time constant of I(A) were accordingly increased after ischemia. The activation curve of I(A) in CA1 neurons shifted to the depolarizing direction at 38 h after ischemia. In granule cells, the amplitude and rising slope of I(A) were significantly increased at 38 h after ischemia; the inactivation curves of I(A) shifted toward the depolarizing direction accordingly at 38 h after ischemia. The I(A) remained unchanged in CA3 neurons after ischemia. The amplitudes of delayed rectifier potassium currents (I(Kd)) in CA1 neurons were progressively increased after ischemia. No significant difference in I(Kd) was detected in CA3 and granule cells at any time points after reperfusion. These results indicated that the voltage dependent potassium currents in hippocampal neurons were differentially altered after cerebral ischemia. The up-regulation of I(A) in dentate granule cells might have protective effects. The increase of I(Kd) in CA1 neurons might be associated with the neuronal damage after ischemia.
短暂性前脑缺血后2 - 3天，海马体中的CA1锥体神经元死亡，而齿状回中的CA3锥体神经元和颗粒细胞仍能存活。兴奋性毒性是缺血性细胞死亡的主要原因，钾电流在调节神经元兴奋性中起重要作用。本研究比较了缺血后不同时间间隔急性分离的海马神经元中钾电流的变化。在CA1神经元中，快速失活钾电流（I(A)）的幅度在缺血后14小时显著增加，并在38小时恢复到对照水平；缺血后I(A)的上升斜率和衰减时间常数相应增加。CA1神经元中I(A)的激活曲线在缺血后38小时向去极化方向移动。在颗粒细胞中，缺血后38小时I(A)的幅度和上升斜率显著增加；缺血后38小时I(A)的失活曲线相应地向去极化方向移动。缺血后CA3神经元中的I(A)保持不变。缺血后CA1神经元中延迟整流钾电流（I(Kd)）的幅度逐渐增加。再灌注后任何时间点，CA3和颗粒细胞中的I(Kd)均未检测到显著差异。这些结果表明，脑缺血后海马神经元中电压依赖性钾电流发生了不同程度的改变。齿状颗粒细胞中I(A)的上调可能具有保护作用。CA1神经元中I(Kd)的增加可能与缺血后的神经元损伤有关。
