Neuroprotection by ATP-dependent potassium channels in rat neocortical brain slices during hypoxia

• Published in: Neuroscience letters Vol. 273; no. 1; pp. 13 - 16
• Main Authors: Garcia de Arriba, Susana, Franke, Heike, Pissarek, Margit, Nieber, Karen, Illes, Peter
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 24-09-1999; Elsevier
• Subjects: Animals; ATP-Binding Cassette Transporters; Biological and medical sciences; Diazoxide; Diazoxide - pharmacology; Hypoglycemic Agents - pharmacology; Hypoxia; Hypoxia, Brain - pathology; Ion Channel Gating - drug effects; K ATP channels; KATP Channels; Male; Medical sciences; Neocortex; Neocortex - pathology; Neurons - metabolism; Neurons - pathology; Neuropharmacology; Neuroprotective agent; Parietal Lobe - drug effects; Parietal Lobe - metabolism; Pharmacology. Drug treatments; Potassium Channels - drug effects; Potassium Channels - physiology; Potassium Channels, Inwardly Rectifying; Pyramidal cells; Pyramidal Cells - drug effects; Pyramidal Cells - pathology; Rats; Rats, Wistar; Somatosensory Cortex - pathology; Tolbutamide; Tolbutamide - pharmacology; Vasodilator Agents - pharmacology; Hypoxia; Diazoxide; Neocortex; Pyramidal cells; K ATP channels; Tolbutamide; Oxygen; Agonist; Rat; Rodentia; Central nervous system; Environmental factor; Ionic channel; Neuroprotective agent; Vertebrata; Mammalia; Animal; Parietal cortex; Antagonist; Potassium; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(99)00603-5

Morphological changes induced by 30 min of hypoxia (incubation in medium saturated with 95% N
2–5% CO
2 instead of the normal 95% O
2–5% CO
2) 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 μM), an agonist of ATP-dependent potassium (K
ATP) channels completely prevented the morphological damage induced by hypoxia, whereas tolbutamide (300 μM), an antagonist of K
ATP channels, was ineffective when given alone. However, tolbutamide (300 μM) co-applied with diazoxide (300 μM), partly reversed the neuroprotective effect of this agonist during hypoxia. In conclusion, K
ATP channels appear to be present on neocortical neurons and their opening counteracts hypoxia-induced cell injury.