Sleep Disorders: Opposing Ions May Be Culprit

The rising sun and moon may not be the only opposite partners when it comes to sleeping and waking.

A research team at Northwestern University recently discovered a pair of opposing ion channels may turn circadian neurons in the brain on and off on a daily cycle.

In a study published in the August 13 issue of Cell, researchers discovered sodium and potassium channels rose and fell in opposition to run the cycle. They were inspired to examine the role of sodium channels 15 years ago, by a mutated fruit fly.

“Our starting point for this research was mutant flies missing a sodium channel who walked in a halting manner and had poor circadian rhythms,” said Ravi Allada, MD, in a news release. Allada is professor and chair of neurobiology in the Weinberg College of Arts and sciences at Northwestern University.

High sodium channel activity in these neurons turns the cells on and wakes the animal, while potassium channel activity remains low. At night, the pattern is reversed. High potassium channel activity turns off the neuronal activity, allowing the animal to sleep.

The team likens the mechanism to the pedals of a bicycle. One pedal is up while the other is down over a 24-hour day, alternately exciting and silencing the neurons.

Allada and his colleagues observed this cycle in two completely different species —the fruit fly and the mouse.

This suggests the underlying mechanism controlling our sleep-wake cycle is ancient,” Allada said in a news release. “This oscillation mechanism appears to be conserved across several hundred million years of evolution. And if it’s in the mouse, it is likely in humans, too.”

“What is amazing is finding the same mechanism for sleep-wake cycle control in an insect and a mammal,” Matthieu Flourakis, PhD, lead author, said in the release. “Mice are nocturnal and flies are diurnal … but their sleep-wake cycles are controlled the same way.”

A better understanding of this mechanism could lead to new drug targets to address disturbances of the sleep-wake cycle, such as jet lag, shiftwork, and circadian disorders. It may become possible to reset a person’s internal clock to match his or her situation.