Enhancement in activities of large conductance calcium-activated potassium channels in CA1 pyramidal neurons of rat hippocampus after transient forebrain ischemia
Enhancement in activities of large conductance calcium-activated potassium channels in CA1 pyramidal neurons of rat hippocampus after transient forebrain ischemia
复制标题
DOI：
10.1016/s0006-8993(00)02923-1
复制
发表时间：
2000-11-24
期刊：
影响因子：
2.9
通讯作者：
Tong, ZQ
中科院分区：
文献类型：
--
作者：
Gong, LW;Gao, TM;Tong, ZQ
已有报道称，短暂性前脑缺血后，大鼠海马CA1锥体细胞的神经元兴奋性持续抑制，且快速后超极化（fAHP）振幅升高。为了了解这些缺血后电生理改变背后的传导机制，我们通过使用膜片钳技术的内外配置，比较了缺血前后与海马急性分离的CA1锥体细胞中大电导Ca2+活化钾（BKCa）通道的活性差异。(1)在内外对称140/140 mM K+斑块中，缺血后神经元BKCa通道的统一电导（295 pS）高于对照神经元（245 pS）；(2)开放概率（P-o）增加e倍的膜去极化在两组间无显著差异，而产生最大P-o的一半所需的膜电位在缺血后更为负，表明通道电压依赖性无明显变化；(3)缺血后激活BKCa通道所需的[Ca2+](i)仅为1 muM，而对照神经元为2 muM，表明缺血后[Ca2+](i)敏感性增加；(4)缺血后BKCa通道的打开时间更长，关闭时间更短，但打开频率与对照组相比无显著差异。本研究结果表明，缺血后CA1锥体神经元BKCa通道活性的增强可能是缺血后神经元兴奋性下降和fAHP升高的部分原因。(C) 2000 Elsevier Science B.V.版权所有
It has been reported previously that the neuronal excitability persistently suppresses and the amplitude of fast afterhyperpolarization (fAHP) increases in CA1 pyramidal cells of rat hippocampus following transient forebrain ischemia. To understand the conductance mechanisms underlying these post-ischemic electrophysiological alterations, we compared differences in activities of large conductance Ca2+-activated potassium (BKCa) channels in CA1 pyramidal cells acutely dissociated from hippocampus before and after ischemia by using inside-out configuration of patch clamp techniques. (1) The unitary conductance of BKCa channels in post-ischemic neurons (295 pS) was higher than that in control neurons (245 pS) in symmetrical 140/140 mM K+ in inside-out patch; (2) the membrane depolarization for an e-fold increase in open probability (P-o) showed no significant differences between two groups while the membrane potential required to produce one-half of the maximum P-o was more negative after ischemia, indicating no obvious changes in channel voltage dependence; (3) the [Ca2+](i) required to half activate BKCa channels was only 1 muM in post-ischemic whereas 2 muM in control neurons, indicating an increase in [Ca2+](i) sensitivity after ischemia; and (4) BKCa channels had a longer open time and a shorter closed rime after ischemia without significant differences in open frequency as compared to control. The present results indicate that enhanced activity of BKCa channels in CA1 pyramidal neurons after ischemia may partially contribute to the post-ischemic decrease in neuronal excitability and increase in fAHP. (C) 2000 Elsevier Science B.V. All rights reserved.