摘要
为探讨钾通道参与神经元凋亡的可能机制 ,在星形孢菌素 (STS)诱导的培养海马神经元凋亡模型上 ,研究了凋亡时神经细胞容积的动态变化及钾通道在其中的作用 .实验结果显示 ,钾通道阻断剂四乙铵或升高细胞外K+ 均能够明显抑制STS诱导的神经元凋亡 ,并且大电导钙激活钾通道 (BK)选择性阻断剂iberiotoxin和paxilline具有同样程度的抗细胞凋亡作用 ,表明钾通道 (可能主要是BK通道 )参与了STS诱导的培养海马神经元凋亡 .在STS诱导神经元凋亡的早期就出现了细胞容积的显著减少 ,而钾通道阻断剂或升高细胞外K+ 均可阻断该细胞容积减少 .研究结果提示细胞内钾离子的外流可能参与了凋亡性细胞容积减少 ,这也可能是钾通道介导细胞凋亡的重要机制之一 .
It has been reported that activation of potassium channel is involved in the apoptosis of hippocampal neurons induced by in vivo ischemia and in vitro hypoxia. Recently, cell shrinkage is proposed as an early prerequisite to apoptotic events leading to cell death. To understand the mechanism underlying potassium channel-mediated neuronal apoptosis, the temporal changes in neuronal cell body volume and the involvement of potassium channel in the apoptotic volume decrease were examined in a model of staurosporine (STS)-induced apoptosis of Cultured hippocampal neurons. Nonselective potassium channel blocker tetraethylammonium (TEA) or raising extracellular K+ concentration significantly prevented STS-induced neuronal cell death. A similar neuroprotection was also observed by treatment with the selective high-conductance calcium-activated potassium channel (BK) blockers iberiotoxin and paxilline. These results indicate that potassium channels, especially BK channels, contribute to STS-induced neuronal apoptosis. Moreover, STS induced an early cell body volume decrease and this cell shrinkage was completely blocked by TEA or high extracellular K+. It is suggested that potassium efflux may be involved in the apoptotic volume decrease, which is probably one of the mechanisms underlying mediation of neuronal apoptosis by potassium channel.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2003年第5期749-754,共6页
Progress In Biochemistry and Biophysics
基金
国家杰出青年基金 ( 3 0 12 5 0 13 )
军队杰出青年基金 ( 0 1J0 0 9)
广东省自然科学基金团队项目 ( 10 717)
教育部长江学者奖励计划资助项目~~
关键词
钾通道
培养
大鼠
海马神经元
凋亡性容积减少
细胞凋亡
hippocampus
neuron
apoptotic volume decrease (AVD)
staurosporine (STS)
potassium channel
