Glucose and sulfonylureas modify different phases of the membrane potential change during hypoxia in rat hippocampal slices.
Intracellular recording during hypoxia in submerged hippocampal slices revealed an initial hyperpolarization with decreased membrane input resistance followed by complete depolarization. Glibenclamide (1 microM) reduced and tolbutamide (400 microM) completely blocked the hypoxic hyperpolarization and the accompanying increase in conductance. Neither glibenclamide nor tolbutamide altered the time to 25 or 50% depolarization. Sulfonylurea-treated slices completely depolarized during 10 min of hypoxia and did not recover upon reoxygenation. In contrast, 11 mM glucose had no effect on hypoxic hyperpolarization or conductance, but it significantly slowed hypoxic depolarization. In half of the intracellular recordings made during high glucose hypoxia, the membrane potential and input resistance returned during reoxygenation. Extracellular recordings were used to evaluate the effect of sulfonylureas and high glucose on acute neuronal survival from hypoxia. Glibenclamide (0.1-5 microM) did not change the survival rate of slices exposed to hypoxia, whereas, high glucose (11 and 40 mM) dramatically improved the recovery of population spikes during reoxygenation. These findings support the hypothesis that an ATP-sensitive K+ channel mediates hypoxic hyperpolarization, but these channels are not regulated by glucose in the brain as in pancreatic islet-cells. These results also suggest that high glucose protects hippocampal slices from hypoxia by slowing the hypoxia-induced depolarization.
Grigg
J J
JJ
Department of Pharmacology, University of Illinois Medical College, Chicago 60612.
Anderson
E G
EG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D013453:Sulfonylurea Compounds; D014044:Tolbutamide; D005947:Glucose; D005905:Glyburide