Transient forebrain ischemia induces persistent hyperactivity of large conductance Ca2+-activated potassium channels via oxidation modulation in rat hippocampal CA1 pyramidal neurons
Transient forebrain ischemia induces persistent hyperactivity of large conductance Ca2+-activated potassium channels via oxidation modulation in rat hippocampal CA1 pyramidal neurons
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DOI：
10.1046/j.1460-9568.2002.01908.x
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Tong, ZQ
中科院分区：
文献类型：
--
作者：
Gong, LW;Gao, TM;Tong, ZQ
本研究探讨了大电导，钙激活钾（BKCa）通道的活动在缺血后CA 1锥体神经元在再灌注后2，6，24和48小时的时间变化。这些变化的活动和可能的细胞机制进行了检查，使用内面向外配置的膜片钳。缺血后BKCa通道的单位电导在再灌注后2 h短暂增加至对照的119%，此后恢复至对照水平。缺血后CA 1神经元BKCa通道的[Ca ~（2+）]（i）敏感性持续增加，再灌注后6 h达到最高，而通道电压依赖性无明显变化。动力学分析表明，缺血后BKCa通道活性的增强是由于开放时间延长和关闭时间缩短，因为缺血后开放频率没有显著变化。在正常的CA 1神经元中，谷胱甘肽显著增加BKCa通道活性，而在缺血后的CA 1神经元中，还原型谷胱甘肽通过降低该通道对[Ca 2 + ]（i）的敏感性而导致BKCa通道活性降低。用另一种氧化还原对DTNB和DTT也观察到对缺血后BKCa通道的类似调节作用，表明缺血后BKCa通道功能的氧化调节。本研究结果表明，持续增强的BKCa通道的活性，可能通过氧化的通道，在postisemic CA 1锥体神经元可能占缺血后神经元兴奋性下降，增加fAHP。缺血诱导的BKCa通道活性增强也可能与缺血后神经元损伤有关。
The present study examined temporal changes in activity of large conductance, Ca2+ -activated potassium (BKCa) channels in postischemic CA1 pyramidal neurons at 2, 6, 24 and 48 h after reperfusion. These changes in activity and possible cellular mechanisms were examined using the inside-out configuration of patch clamp. The unitary conductance of postischemic BKCa channels increased transiently to 119% of the control at 2 h after reperfusion, and recovered to the control level thereafter. A persistent increase in [Ca2+ ](i) sensitivity of BKCa channels was observed in postischemic CA1 neurons with the maximal sensitivity to [Ca2+ ](i) at 6 h after reperfusion while channel voltage- dependence showed no obvious changes. Kinetic analyses showed that the postischemic enhancement of BKCa channel activity was due to longer open times and shorter closed times as there was no significant changes in opening frequency after ischemia. Glutathione disulphide markedly increased BKCa channel activity in normal CA1 neurons, while reducing glutathione caused a decrease in BKCa channel activity by reducing the sensitivity of this channel to [Ca2+ ](i) in postischemic CA1 neurons. Similar modulatory effects on postischemic BKCa channels were also observed with another redox couple, DTNB and DTT, suggesting an oxidation modulation of BKCa channel function after ischemia. The present results indicate that a persistent enhancement in activity of BKCa channels, probably via oxidation of channels, in postischemic CA1 pyramidal neurons may account for the decrease in neuronal excitability and increase in fAHP after ischemia. The ischemia-induced augmentation in BKCa channel activity may be also associated with the postischemic neuronal injury.