Differential Effects of Glucose and Lactate on Glucosensing Neurons in the Ventromedial Hypothalamic Nucleus

Differential Effects of Glucose and Lactate on Glucosensing Neurons in the Ventromedial Hypothalamic Nucleus Z. Song and V.H. Routh From the Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey Address correspondence and reprint requests to Vanessa H. Routh, PhD, Department of Pharmacology and Physiology, New Jersey Medical School (UMDNJ), P.O. Box 1709, Newark, NJ 07101-1709. E-mail: routhvh{at}umdnj.edu 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. ACSF, artificial cerebrospinal fluid CNS, central nervous system KATP channel, ATP-sensitive K+ channel VMH, ventromedial hypothalamus VMN, ventromedial hypothalamic nucleus Footnotes Accepted September 20, 2004. Received June 9, 2004. DIABETES