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Researchers from University of Wisconsin Medical School have identified a single gene mutation that has a powerful effect on the amount of time fruit flies sleep. In its normal state, the Drosophila (fruit fly) gene, called Shaker, produces an ion channel that controls the flow of potassium into cells, a process that critically affects, among other things, electrical activity in neurons. A handful of recent studies suggest that potassium channels are also involved in the generation of sleep in humans.
Published in this month's Nature, the finding points to novel approaches to treating sleep irregularities in humans-from promoting restorative sleep to prolonging wakefulness. This research offers the possibility of developing a new class of compounds that could affect potassium channels in the brain rather than other brain chemical systems targeted currently.
Most people sleep seven to eight hours a night, and if they are deprived of sleep, their cognitive performance suffers greatly. However, a few people do well with just three or four hours of sleep-a trait that seems to run in families. Understanding the genes that underlie this phenomenon can shed light on the mechanisms and functions of sleep.
The Wisconsin study focuses on factors that control sleep duration as opposed to the timing of when sleep occurs, which is regulated by the circadian system, The key molecular mechanisms controlling the circadian timing of sleep are well understood, but details about the homeostatic mechanism that regulates the amount of sleep have been unclear.
Like humans, fruit flies generally are quiet and immobile for between six and 12 hours each night and lose most of their ability to respond to stimuli, the researchers found. When deprived of sleep, humans and their winged counterparts rebound on the following night by sleeping longer and more deeply. Flies also sleep more in their youth than later in life, when their sleep is fragmented, as with humans.
In mammals the changes produce hallmark waves, or oscillations of groups of neurons, easily detected by EEG. The waves are slower during deep sleep and faster during waking times. One way of getting from the faster to the slower state is by opening ion channels, allowing potassium to flow through them. The Wisconsin researchers hypothesize that if you don't have potassium channels, you won't get slow waves. The cell membrane will remain activated, preventing long periods of deep, non-REM sleep. The researchers found that the fly research translates to humans even more than they thought it would. Humans have the same kind of genes and potassium channels and slow waves must be generated by changes in the excitability of neuron cell membranes. Essentially, potassium changes may have a tremendous affect on sleep in humans.
Sleep is a highly complex activity and probably involves many genes, some of which are more influential than others, The researchers believe this gene is very powerful because it acts on the final common pathway and has the ability to change the excitability of neurons.
Nature article
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