Now, in an article in the June 1, 2006, Neuron, Denis Burdakov of the University of Manchester and his colleagues have pinpointed how glucose inhibits neurons that are key to regulating wakefulness. In the process, they have discovered a role for a class of potassium ion channels whose role has remained largely unknown. Such ion channels are porelike proteins in the cell membrane that affect cellular responses by controlling the flow of potassium into the cell.
The researchers set out to discover how glucose inhibits a particular class of glucose-sensing neurons that produce tiny proteins called orexins, which are central regulators of states of consciousness.
Wrote Burdakov and colleagues, "These cells are critical for responding to the ever-changing body-energy state with finely orchestrated changes in arousal, food seeking, hormone release, and metabolic rate, to ensure that the brain always has adequate glucose."
Malfunction of orexin neurons can lead to narcolepsy and obesity, and researchers have also found evidence that orexin neurons play a role in learning, reward-seeking, and addiction, wrote the researchers.
"Considering these crucial roles of orexin neurons, their recently described inhibition by glucose is likely to have considerable implications for the regulation of states of consciousness and energy balance," wrote Burdakov and his colleagues. "However, as in other glucose-inhibited neurons, it is unknown how glucose suppresses the electrical activity of orexin cells." What’s more, they wrote, "Because the sensitivity of orexin cell firing to the small changes in extracellular glucose that occur between normal meals has never been tested, the daily physiological relevance of their glucose sensing is also unknown."
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 tunes arousal and metabolism according to body-energy levels."
Heidi Hardman | EurekAlert!
Warming ponds could accelerate climate change
21.02.2017 | University of Exeter
An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
21.02.2017 | Earth Sciences
21.02.2017 | Medical Engineering
21.02.2017 | Trade Fair News