Neuroprotection by ATP-dependent potassium channels in rat neocortical brain slices during hypoxia.
Morphological changes induced by 30 min of hypoxia (incubation in medium saturated with 95% N2-5% CO2 instead of the normal 95% O2-5% CO2) were investigated in neurons (layers II/III of the parietal cortex) of rat neocortical brain slices. The cells were identified as intact, reversibly or irreversibly injured. As expected, hypoxia decreased the number of intact cells and increased the number of irreversibly injured cells. Pretreatment of slices with diazoxide (300 microM), an agonist of ATP-dependent potassium (KATP) channels completely prevented the morphological damage induced by hypoxia, whereas tolbutamide (300 microM), an antagonist of KATP channels, was ineffective when given alone. However, tolbutamide (300 microM) co-applied with diazoxide (300 microM), partly reversed the neuroprotective effect of this agonist during hypoxia. In conclusion, KATP channels appear to be present on neocortical neurons and their opening counteracts hypoxia-induced cell injury.
Garcia de Arriba
S
S
Institut für Pharmakologie und Toxikologie, Universität Leipzig, Germany.
Franke
H
H
Pissarek
M
M
Nieber
K
K
Illes
P
P
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000473:pathology*; D015640:Ion Channel Gating / Q000187:drug effects; D054086:KATP Channels; D008297:Male; D019579:Neocortex / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000473:pathology; D014044:Tolbutamide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D014044:Tolbutamide; D003981:Diazoxide