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.