Voltage-dependent potassium channels are involved in glutamate-induced apoptosis of rat hippocampal neurons.
The role of voltage-dependent potassium channel currents in glutamate-treated rat hippocampal neurons was investigated. Cell viability was evaluated by MTT reduction assay and morphological changes. Apoptosis was detected by Hoechst33342 staining with fluorescent microscopy and propidium iodide staining with flow cytometry. Membrane potassium channel currents were recorded with whole-cell patch clamp recordings. Results showed that after shortly exposed to glutamate, about 25 and 50% cells died in 3 h and 24 h, respectively. Meanwhile, the enhancement of IK was observed within 6 h after the glutamate insult. TEA selectively blocked IK and significantly reduced cell apoptosis. IA did not change in the insult though 4-AP, the blocker of this current, showed a protective effect against the injury. These data were in consistent with the hypothesis that K+ efflux contributed to glutamate-triggered apoptosis and IK channels might have a therapeutic effect on the treatment of cerebral ischemia.
Zhao
Yu-Ming
YM
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Sun
Li-Na
LN
Zhou
Hong-Yi
HY
Wang
Xiao-Liang
XL
D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles; D004396:Coloring Agents; D051668:Delayed Rectifier Potassium Channels / Q000502:physiology; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011419:Propidium; D051381:Rats; D017208:Rats, Wistar
D001562:Benzimidazoles; D004396:Coloring Agents; D051668:Delayed Rectifier Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011419:Propidium; D018698:Glutamic Acid; C017807:bisbenzimide ethoxide trihydrochloride