Ischemic preconditioning in the hippocampus of a knockout mouse lacking SUR1-based K(ATP) channels.
OBJECTIVE
ATP-sensitive K+ (K(ATP)) channels have been implicated in the mechanism of neuronal ischemic preconditioning. To evaluate the role of neuronal/beta-cell-type K(ATP) channels, SUR1 null (Sur1KO) mice lacking (K(IR)6.x/SUR1)(4) K(ATP) channels were subjected to a preconditioning protocol with the use of double carotid occlusion.


METHODS
Wild-type C57BL/6 and Sur1KO mice were subjected to a double carotid block for 40 minutes with or without a 20-minute preconditioning block. After a 10-day reperfusion period, damage was assessed histologically in the hippocampal CA1, CA2, and CA3 areas and in the dentate gyrus. The neuroprotective effects of intracerebroventricular injections of diazoxide, which selectively affects mitochondria versus opening SUR1-type K(ATP) channels, and 5-hydroxydecanoate, a selective blocker of mitoK(ATP) channels, were evaluated with the same protocol.


RESULTS
Neurons in the CA1 region of both Sur1KO and wild-type animals subjected to a 20-minute ischemic insult were protected equally from neuronal damage produced by a subsequent 40-minute ischemic period. Pretreatment with diazoxide protected both Sur1KO and wild-type neurons, while 5-hydroxydecanoate augmented neurodegeneration in both strains of animals when administered before a 20-minute bout of ischemia.


CONCLUSIONS
SUR1-based K(ATP) channels are not obligatory for neuronal preconditioning or augmentation of neurodegeneration by 5-hydroxydecanoate.
Muñoz
Alvaro
A
Department of Medicine, Baylor College of Medicine, Houston, Tex 77030, USA.
Nakazaki
Mitsuhiro
M
Goodman
J Clay
JC
Barrios
Roberto
R
Onetti
Carlos G
CG
Bryan
Joseph
J
Aguilar-Bryan
Lydia
L
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000627:therapeutic use; D006624:Hippocampus / Q000098:blood supply* / Q000473:pathology; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia / Q000209:etiology; D019194:Ischemic Preconditioning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D026902:Potassium Channel Blockers / Q000627:therapeutic use; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology*
D003652:Decanoic Acids; D006880:Hydroxy Acids; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D003981:Diazoxide