title: The protective roles of mitochondrial ATP-sensitive potassium channels during hypoxia-ischemia-reperfusion in brain.
abstract: The role of ATP-sensitive potassium (K(ATP)) channels in cerebral ischemia-reperfusion has been well documented. K(ATP) channel openers protect neuron by mimicking ischemic preconditioning. However, the different protection between the mitochondrial and sarcolemma K(ATP) openers has been seldom studied. In the experiment, we investigated the effects of K(ATP) channel openers diazoxide and pinacidil on the hypoxia-ischemia-reperfusion in cultured hippocampal neurons and gerbil brain. The cultured hippocampal neurons and gerbil brain were pretreated with diazoxide or pinacidil before oxygen-glucose deprivation (OGD) and cerebral ischemia-reperfusion, respectively. Survival rate, apoptosis rate and lactate dehydrogenase (LDH) releasing after the reperfusion were subsequently detected. Then the subunits mRNA was detected by RT-PCR. The survival rate and LDH content in diazoxide group increased more than that in pinacidil group (86.21±2.73% vs. 78.59±1.94%, P<0.05; 133.29±15.00 U/L vs. 193.47±3.39 U/L, P<0.01). The apoptosis rate in diazoxide group decreased significantly more than that in pinacidil group (23.82±0.14% vs. 37.05±0.67%, P<0.01). Diazoxide pretreatment increased the expression of Kir6.1 mRNA obviously. The results suggested that mitoK(ATP) channels opener diazoxide played a major protective role on cerebral ischemia-reperfusion. Furthermore, diazoxide might become a new treatment for cerebral ischemia diseases through increasing the expression of Kir6.1 mRNA.
authors.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Fuxing Road 28, Beijing 100853, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Zhu
authors.forename: Guo-Zheng
authors.initials: GZ
authors.lastname: Wang
authors.forename: Tian-Zheng
authors.initials: TZ
authors.lastname: Deng
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Mo-Han
authors.initials: MH
authors.lastname: Liu
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000502:physiology*; D004195:Disease Models, Animal; D005849:Gerbillinae; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D054086:KATP Channels / Q000235:genetics / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D054086:KATP Channels