Activation of mitochondrial ATP-sensitive potassium channels prevents neuronal cell death after ischemia in neonatal rats

被引：59

作者：

Rajapakse, N ^{[1
]}

Shimizu, K ^{[1
]}

Kis, B ^{[1
]}

Snipes, J ^{[1
]}

Lacza, Z ^{[1
]}

Busija, D ^{[1
]}

机构：

[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA

来源：

NEUROSCIENCE LETTERS | 2002年 / 327卷 / 03期

关键词：

diazoxide; hypoxia-ischemia; 5-hydroxydecanoic acid; potassium channels;

D O I：

10.1016/S0304-3940(02)00413-5

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Activation of mitochondrial ATP-sensitive potassium channels (mK(ATP)) has been shown to protect against cell death following ischemia/reperfusion in the heart but not in brain. We examined whether mK(ATP) activation with diazoxide (DIZ) prevents neuronal cell death following hypoxia-ischemia (HI) in 7-day-old rat pups. Rat pups were subjected to HI (left carotid ligation; 8% O-2; 2.5 h), following administration of vehicle, 1.9 mg/kg DIZ, 3.8 mg/kg DIZ or DIZ plus 10 mg/kg 5-hydroxydecanoic acid (mK(ATP) antagonist). Total infarct volume was reduced from 99.8+/-2.7% in vehicle animals to 80.6+/-4.2% in 3.8 mg/kg DIZ treated animals (n = 85, P < 0.05). Western blotting showed K-ATP subunits concentrated in mitochondria. Fluorescent studies indicated DIZ directly depolarized the mitochondria. In conclusion, selective opening of mK(ATP) prior to Hl results in neuroprotection in immature rats. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：208 / 212

页数：5

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