We found previously that VMN glucosensing neurons are inhibited when extracellular glucose is either increased or decreased (Routh et al., SFN Abst. 25:416,99). The inhibitory effect of decreasing glucose was reversed by tolbutamide, suggesting the involvement of the ATP sensitive K+ (KATP) channel. This study was performed to determine the mechanism responsible for the inhibitory effect of high extracellular glucose. Slices 350 microns thick were sectioned through the VMN of brains of 14-21 d inbred diet-resistant (DR) Sprague-Dawley rats. Slices were then perfused with artificial CSF + 2.5 mM glucose. Current clamp recordings were made using conventional whole cell patch clamp with ATP (2 mM) in the patch pipette. Six of 42 VMN neurons hyperpolarized and decreased their action potential frequency when extracellular glucose was raised from 2.5 to 5 or 10 mM. Similarly, 8 of 52 VMN neurons hyperpolarized and decreased their action potential frequency when extracellular glucose was decreased from 2.5 to 0.1...