In their experiments, the researchers engineered mice to produce a fluorescent protein only in orexin neurons. Thus, the researchers could isolate the neurons in brain slices from the mice and perform precise biochemical and electrophysiological studies to explore how glucose acted on those neurons. In particular, the researchers performed experiments in which they exposed the neurons to the subtle changes in glucose levels known to occur in daily cycles of hunger and eating.
Their experiments showed that glucose inhibits orexin neurons by acting on a class of potassium ion channels known as "tandem pore" channels, about which little was known.
"Together, these results identify an unexpected physiological role for the recently characterized [tandem pore potassium] channels and shed light on the long-elusive mechanism of glucose inhibition, thus providing new insights into cellular pathways regulating vigilance states and energy balance," wrote Burdakov and colleagues.
"These results provide evidence that the firing rate of orexin cells is sensitive to changes in glucose that correspond to fluctuations occurring normally during the day and also show that the same electrical mechanism is involved in sensing both subtle and extreme changes in glucose," they wrote.
What's more, they wrote, their finding that subtle changes in glucose levels affect firing of orexin "raises the possibility that, besides being important for adaptive responses to starvation, modulation of orexin cells by glucose has a much wider behavioral role, contributing to the continuous daily readjustments in the level of arousal and alertness."
The researchers concluded that their findings "provide important new insights into how the brain t