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.