Reactive oxygen species mediate the neuroprotection conferred by a mitochondrial ATP-sensitive potassium channel opener during ischemia in the rat hippocampal slice.
Reactive oxygen species (ROS) are known to mediate the protection conferred by the opening of mitochondrial ATP-sensitive potassium channels (mitoK(ATP)) during ischemia in heart, but this has not been demonstrated in brain. The present study examined whether ROS mediate the neuroprotection conferred by a mitoK(ATP) opener during ischemia in rat hippocampal slices. Ischemia was simulated by oxygen and glucose deprivation. The direct current potential and population spike were recorded in the stratum pyramidale of the CA1 region, and lactate dehydrogenase (LDH) efflux into the medium was assayed. ROS generation was measured spectrophotofluorometrically. Pretreatment of slices with diazoxide (DIA, 300 microM), a mitoK(ATP) opener, (i) prolonged the latency to ischemic depolarization and decreased its amplitude, (ii) delayed the onset of population spike disappearance and enhanced its recovery after reperfusion, (iii) decreased LDH efflux and (iv) increased ROS levels. The effects induced by DIA were attenuated by 5-hydroxydecanoic acid (200 microM), a mitoK(ATP) blocker. Pretreatment with N-2-mercaptopropionyl glycine (MPG, 500 microM), a ROS scavenger, also abrogated the effects induced by DIA, while treatment with MPG alone had no effect during normoxia and ischemia. These results indicate that ROS participate in the neuroprotection conferred by a mitoK(ATP) opener during ischemia.
Liang
Hua-Wei
HW
Department of Physiology, Zhejiang University School of Medicine, 353# Yan-an Road, Hangzhou 310031, China.
Xia
Qiang
Q
Bruce
Iain C
IC
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D003981:Diazoxide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D018696:Neuroprotective Agents; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D003981:Diazoxide