How do we fall asleep and wake up? Scientists uncover key mechanism

Published in the journal Nature Communications, the study suggests that BK channels in the suprachiasmatic nucleus (SCN) – located in the hypothalamus of the brain – regulate the “switch” between sleep and wakefulness.

[The BK channels of mice during sleep-wake cycles]

BK channels are part of the ion channel family. In the brain, they are responsible for conducting electrical current, enabling communication between neurons, or brain cells.

According to study co-author Prof. Andrea Meredith – of the University of Maryland School of Medicine – and colleagues, these channels are particularly active in the SCN, which is the brain region involved in the regulation of circadian rhythms; it tells us when to go to sleep, how long to sleep for and when to get up.

Unfortunately, some people’s circadian rhythm, or body clock, is out of sync, which can lead to sleep disorders, such as insomnia, jet lag and seasonal affective disorder.

To find out if BK channels in the SCN play a role in circadian rhythm, Prof. Meredith and colleagues analyzed the SCN of mice. The sleep pattern of mice is opposite to that of humans; they sleep during the day but stay awake at night.

Mice unable to inactivate BK channel showed increased wakefulness

Some of the mice analyzed had been genetically modified so that their BK channels in the SCN could not be inactivated. In order to record activity in the BK channels of these mice – as well as the BK channel activity of normal mice – the team implanted electrodes in SCN neurons of the rodents.

Among normal mice, the team found that during the day, when the rodents sleep, the BK channels were inactive, but they were active during nighttime, when mice are normally awake.

An inactive daytime BK channel triggered higher neuronal activity in the SCN of mice, which led to sleep, but an active nighttime BK channel reduced neuronal activity, triggering wakefulness.

The team reached this conclusion after identifying lower neuronal activity in the mice that were unable to inactivate their BK channels, which they found led to increased daytime wakefulness.

The researchers note that, despite mice having an opposite sleep pattern to us, the association between neuronal activity and sleep-wake cycles is similar in both mice and humans.

Study shows BK channels are key for regulating sleep-wake cycles

According to the team, this study is the first to show that inactivation of BK channels is key for encoding the brain’s circadian rhythm, regulating sleep-wake cycles.

Previously, studies have suggested that the number of ion channels present on the surface of SCN cells is responsible for neuronal activity that regulates circadian rhythm. This latest research, however, shows that it is the activation – and inactivation – of BK channels that is responsible.

Prof. Meredith says:

“We knew that BK channels were widely important throughout the body. But now we have strong evidence that they are specifically and intrinsically involved in the wake-sleep cycle. That’s really exciting.”

The team says the findings could pave the way for the development of drugs that target circadian rhythms, which could help treat sleep disorders, jet lag and other conditions caused by body clock dysfunction.

Earlier this month, Medical News Today reported on a study suggesting insomnia may be triggered by a reduction in white matter in specific areas of the brain linked to sleep and wakefulness, cognitive function and sensorimotor function.