Contribution of Kv channel subunits to glutamate-induced apoptosis in cultured rat hippocampal neurons.
Potassium channel dysfunction has been implicated in apoptosis in many pathological conditions. However, which Kv channel subunit is involved in glutamate-induced apoptosis remains unknown. In this study, the contributions of nine Kv alpha and three Kv beta subunits to glutamate-induced hippocampal neuronal apoptosis were investigated. Results showed that neuronal apoptosis was not obvious with 12 hr incubation of glutamate but increased markedly after 18 hr, which was attenuated by the Kv channel blocker TEA. Among all the Kv subunits investigated, gene and protein expression of Kv2.1 increased significantly before the appearance of neuronal apoptosis, whereas the Kv1.1 mRNA level decreased quickly, and protein expression was reduced gradually after the insult. Seven other Kv alpha subunits and three Kv beta subunits were not obviously affected over time. In addition, Kv1.1 overexpression could reduce glutamate-induced hippocampal neuronal apoptosis. Therefore, the alterations of Kv1.1 and Kv2.1 might contribute to glutamate-induced toxicity in hippocampal neurons. These findings suggest that these two Kv channel subunits may represent potential therapeutic targets for neuropathological conditions in which glutamate-induced toxicity is thought to contribute to neuronal dysfunction.
Shen
Qi-Jun
QJ
School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China.
Zhao
Yu-Ming
YM
Cao
Dong-Xu
DX
Wang
Xiao-Liang
XL
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D053938:DNA Fragmentation; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051662:Kv1.1 Potassium Channel / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051669:Shab Potassium Channels / Q000378:metabolism*
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D051662:Kv1.1 Potassium Channel; D018698:Glutamic Acid