Tolbutamide suppresses anoxic outward current of hippocampal neurons.
In hippocampal slices, 2-3 min of hypoxia often evokes a hyperpolarisation or outward current. In the presence of tetrodotoxin and kynurenic acid (to minimize indirect effects of the drugs), we applied two sulphonylureas to detect a possible involvement of ATP-sensitive K (KATP) channels. In all 9 cells tested, tolbutamide (TOLB, 0.1-1 mM) greatly reduced both the hypoxic current (by 81.3 +/- 9.4%) and the conductance increase (by 77.2 +/- 10.2%). By contrast, glibenclamide (GLIB, 10-30 microM) tested on 5 cells, had no comparable effects. We therefore conclude that if KATP channels play a role in the hypoxic response, they are likely to be of the low affinity type found in neocortical and hypothalamic neurons.
Godfraind
J M
JM
Anaesthesia Research Department, McGill University, Montréal, Qué., Canada.
Krnjević
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D007736:Kynurenic Acid; D005905:Glyburide