Novel role of KCNQ2/3 channels in regulating neuronal cell viability.
Novel role of KCNQ2/3 channels in regulating neuronal cell viability.
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DOI：
10.1038/cdd.2010.120
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发表时间：
2011-03
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
某些K+通道的过度激活可以介导细胞内K+耗竭，这是凋亡级联的早期离子事件。本研究探讨了KCNQ2/3通道或m通道（也称为Kv7.2/7.3通道）在促凋亡过程中的可能作用。全细胞记录显示，培养海马神经元的m电流（212±31 pA或10.5±1.5 pA/pF）明显高于培养皮层神经元（47±21 pA或2.4±0.8 pA/pF）。KCNQ2/3通道打开剂n -乙基马来酰亚胺（NEM）和氟吡汀在海马培养中引起剂量依赖性的K+外排、细胞内K+耗竭和细胞死亡，而在皮质培养中NEM诱导的细胞死亡很少。联合应用KCNQ通道抑制剂XE991 （10 μM）或升高细胞外钾可拮抗nem诱导的细胞死亡。支持介导凋亡的作用，在CHO细胞中表达KCNQ2或KCNQ2/3通道启动caspase-3激活。同样，在海马培养物中应用NEM （20 μM）同样引起caspase-3激活。NEM增加细胞外信号调节蛋白激酶1和2 （ERK1/2）的表达，诱导线粒体膜去极化，细胞色素c释放，凋亡复合物的形成，以及AIF易位到细胞核。所有这些事件都通过阻断KCNQ2/3通道而减弱。这些发现为KCNQ2/3通道可能是神经元凋亡的重要调节因子提供了新的证据。
Over-activation of certain K+ channels can mediate intracellular K+ depletion, which is an early ionic event in apoptotic cascade. The present investigation examined a possible role of the KCNQ2/3 channel or M-channel (also named Kv7.2/7.3 channels) in the pro-apoptotic process. Whole-cell recordings detected significantly greater M-currents (212 ± 31 pA or 10.5 ± 1.5 pA/pF) in cultured hippocampal neurons than in cultured cortical neurons (47 ± 21 pA or 2.4 ± 0.8 pA/pF). KCNQ2/3 channel openers N-ethylmaleimide (NEM) and flupirtine caused dose-dependent K+ efflux, intracellular K+ depletion, and cell death in hippocampal cultures while little cell death was induced by NEM in cortical cultures. The NEM-induced cell death was antagonized by co-applied KCNQ channel inhibitor XE991 (10 μM), or by elevated extracellular potassium. Supporting a mediating role in apoptosis, expression of KCNQ2 or KCNQ2/3 channels in CHO cells initiated caspase-3 activation. Consistently, application of NEM (20 μM) in hippocampal cultures similarly caused caspase-3 activation. NEM increased the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), induced mitochondrial membrane depolarization, cytochrome c release, formation of apoptosome complex, and AIF translocation into the nucleus. All these events were attenuated by blocking KCNQ2/3 channels. These findings provide novel evidence that KCNQ2/3 channels could be an important regulator in neuronal apoptosis.
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凋亡对细胞死亡的形态学和细胞化学测定。
影响因子：
2.3
作者：
Taatjes, Douglas J.;Sobel, Burton E.;Budd, Ralph C.
通讯作者：
Budd, Ralph C.
影响因子：
4.8
作者：
Sinha, D;Bannergee, S;Levine, JS
通讯作者：
Levine, JS
DOI：
10.1097/00004647-200208000-00005
发表时间：
2002-08-01
影响因子：
6.3
作者：
Lesuisse, C;Martin, LJ
通讯作者：
Martin, LJ
DOI：
10.1016/s0006-291x(02)02017-x
发表时间：
2002-08-30
影响因子：
3.1
作者：
Haase, H;Beyersmann, D
通讯作者：
Beyersmann, D
影响因子：
5.5
作者：
Vervaeke, K.;Gu, N.;Storm, J. F.
通讯作者：
Storm, J. F.