ATP-dependent potassium channel mediates neuroprotection by chemical preconditioning with 3-nitropropionic acid in gerbil hippocampus.
Chemical preconditioning with low dose of 3-nitropropionic acid (3-NPA) prolongs the latency to hypoxic depolarization (HD), which triggers cell death, and also restores the synaptic transmission which disappears during hypoxia in gerbil hippocampal slices. Here we show that these neuroprotective effects are mediated by the activation of K(ATP) channels. Diazoxide, a K(ATP) channel opener, prolonged the latency to HD dose-dependently to the same extent as that of the chemical preconditioning with 3-NPA. Glibenclamide, a K(ATP) channel blocker, abrogated the prolongation of HD with 3-NPA. The hypoxic tolerance of synaptic transmission with 3-NPA was also abolished by glibenclamide. Diazoxide also induced the hypoxic tolerance of synaptic transmission. Theses results suggest that K(ATP) channel is involved in the neuroprotection afforded by the chemical preconditioning.
Nakagawa
Ichiro
I
Department of Neurosurgery, Nara Medical University, Shijo-cho 840, Kashihara 634-8521, Japan.
Nakase
Hiroyuki
H
Aketa
Shuta
S
Kamada
Yoshitaka
Y
Yamashita
Masayuki
M
Sakaki
Toshisuke
T
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019194:Ischemic Preconditioning / Q000379:methods*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D003292:Convulsants; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011422:Propionates; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D003981:Diazoxide; C015392:3-nitropropionic acid; D005905:Glyburide