TOLBUTAMIDE SUPPRESSES ANOXIC OUTWARD CURRENT OF HIPPOCAMPAL-NEURONS

In hippocampal slices, 2-3 min of hypoxia often evokes a hyperpolarisa tion or outward current. In the presence of tetrodotoxin and kynurenic acid (to minimize indirect effects of the drugs), we applied two sulp honylureas to detect a possible involvement of ATP-sensitive K (K(ATP) ) channels. In all 9 cells tested, tolbutamide (TOLB, 0.1-1 mM) greatl y reduced both the hypoxic current (by 81.3 +/- 9.4%) and the conducta nce increase (by 77.2 +/- 10.2%). By contrast, glibenclamide (GLIB, 10 -30 muM) tested on 5 cells, had no comparable effects. We therefore co nclude that if K(ATP) channels play a role in the hypoxic response, th ey are likely to be of the low affinity type found in neocortical and hypothalamic neurons.