K+ channels stimulated by glucose: a new energy-sensing pathway.
Insights into how sugar can turn off cell activity are emerging from studies of hypothalamic neurons. Brain states are coordinated by hypothalamic orexin/hypocretin neurons, whose loss leads to narcoleptic instability of consciousness and inability to rouse when hungry. Recent studies indicate that glucose blocks the electrical activity of orexin cells by opening K+ channels in their membrane. This new energy-sensing mechanism is so sensitive that even small changes in glucose levels, of the type occurring between meals, can turn orexin cells on and off. Glucose-stimulated K+ channels share biophysical properties with "leak" (two-pore domain) K+ channels, the newest and least understood K+ channel family. A hypothesis is outlined whereby the stimulation of brain K+ channels by sugar could relieve stress and enhance reward, although probably at a cost of increased sleepiness.
Burdakov
Denis
D
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, UK. dib22@cam.ac.uk
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D015221:Potassium Channels; D005947:Glucose