title: Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleus.
abstract: Glucose directly alters the action potential frequency of glucosensing neurons in the ventromedial hypothalamic nucleus (VMN). Glucose-excited neurons increase, and glucose-inhibited neurons decrease, their action potential frequency as glucose increases from 0.1 to 2.5 mmol/l. Glucose-excited neurons utilize the ATP-sensitive K(+) channel (K(ATP) channel) to sense glucose, whereas glucose opens a chloride channel in glucose-inhibited neurons. We tested the hypothesis that lactate, an alternate energy substrate, also regulates the action potential frequency of VMN glucose-excited and -inhibited but not nonglucosensing neurons. As expected, lactate reversed the inhibitory effects of decreased glucose on VMN glucose-excited neurons via closure of the K(ATP) channel. Although increasing glucose from 2.5 to 5 mmol/l did not affect the activity of glucose-excited neurons, the addition of 0.5 mmol/l lactate or the K(ATP) channel blocker tolbutamide increased their action potential frequency. In contrast to the glucose-excited neurons, lactate did not reverse the effects of decreased glucose on VMN glucose-inhibited neurons. In fact, it increased their action potential frequency in both low and 2.5 mmol/l glucose. This effect was mediated by both K(ATP) and chloride channels. Nonglucosensing neurons were not affected by lactate. Thus, glucose and lactate have similar effects on VMN glucose-excited neurons, but they have opposing effects on VMN glucose-inhibited neurons.
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School, P.O. Box 1709, Newark, NJ 07101-1709, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.forename: V H
authors.initials: VH
authors.lastname: Routh
mesh_terms: D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: D019344:Lactic Acid; D005947:Glucose