VMN glucosensing neurons alter their firing rate in response to physiologic changes in extracellular glucose. This is mediated in part by the ATP-sensitive K+ (KATP) channel (Routh et al., SFN Abst 25:416, 99) which we found to be defective in inbred DIO-prone vs DR rats (Routh et al., FASEB J. 12(5) A864, 98). To assess whether glucosensing by intact VMN neurons in DIO-prone rats is also dysfunctional, 350 micron slices through the VMN of 14-21d inbred DIO and DR rats were perfused with artificial CSF + 2.5 mM glucose. Current clamp measurements were made using conventional whole cell patch clamp with ATP (2 mM) included in the patch pipette. Decreasing extracellular glucose from 2.5 to 0.1 mM either increased (11 of 52) or decreased (8 of 52) the firing rate of 36% of VMN neurons in DR rats. The latter was reversed by 200 μM tolbutamide (n = 4), suggesting involvement of the KATP channel. Similarly, increasing extracellular glucose from 2.5 to 5 or 10 mM glucose either increased (8 of 42) or decreased (6...