The protective roles of mitochondrial ATP-sensitive potassium channels during hypoxia–ischemia–reperfusion in brain |
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Authors: | Lin Wang Qing-Lei Zhu Guo-Zheng Wang Tian-Zheng Deng Rui Chen Mo-Han Liu Shi-Wen Wang |
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Institution: | 1. Institute of Geriatric Cardiology, Chinese PLA General Hospital, Fuxing Road 28, Beijing 100853, China;2. The 117 Hospital of PLA, Hangzhou 310013, China;3. General Hospital of the Air Force of the Chinese People''s Liberation Army, Beijing 100142, China |
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Abstract: | The role of ATP-sensitive potassium (KATP) channels in cerebral ischemia–reperfusion has been well documented. KATP channel openers protect neuron by mimicking ischemic preconditioning. However, the different protection between the mitochondrial and sarcolemma KATP openers has been seldom studied. In the experiment, we investigated the effects of KATP 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 mitoKATP 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. |
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Keywords: | ATP sensitive potassium channel Hypoxia&ndash ischemia&ndash reperfusion Oxygen-glucose deprivation Pharmacologic preconditioning |
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