In more nerdy news, ever notice how sleepy you get after eating a large meal? It's because of the activity of orexin/hypocretin, a new study indicates. Turns out the hypothalamus, long indicated as a source of the neuronal misfortune that leads to narcolepsy, plays a role in monitoring our blood glucose levels. When the glucose level spikes, like after you eat, the brain's "get food" activities are turned off, and "preserve energy" kicks in -- leading to lethargy and nap-time.
Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K+ (K2P) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca2+, or glucose itself. These results reveal an unexpected energy-sensing pathway in neurons that regulate states of consciousness and energy balance. (Abstract)From ACS:
The article can be found in Neuron 2006, 50, 711–722[the researchers] found that glucose’s effect on the firing rate of the neurons was well matched to the concentrations of blood glucose that typically oscillate between meals.
This provides the strong suggestion of a link between glucose levels in the blood and a corresponding behavioral output: the orexin/hypocretin neurons cannot only sense small changes in glucose levels, but they can respond to those levels by adjusting their firing rate to those levels. This shows that the neurons are capable of being involved in moment-to-moment readjustments of alertness depending on glucose as a guide. Additional work will be needed to confirm that what can be made to occur in isolated cells really does play a physiological role in the whole animal.
As for the precise steps involved, the researchers were able to show that glucose specifically affected a particular ion channel known as the tandem-pore K+ channel in the neuronal cell membrane. This effect was only initiated if glucose was introduced in the external medium. If glucose was added to the interior of the cell, no effects were seen. Glucose, therefore, does not act as an internal messenger. No effects were seen if ATP or Ca2+ ions were added either, leaving the intracellular mechanism a mystery yet to be resolved.
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