There are millions of people who have trouble with transitioning from an asleep to an awake state. Many find it difficult to fall and stay asleep throughout the night, as well as stay awake and alert throughout the day. The neurobiological mechanics of our sleep-wake cycle, or circadian rhythm, has remained largely unknown despite the decades of research performed on the subject.
New research out of the University of Maryland School of Medicine (UM SOM) has recently found a key pathway to these processes; specifically, the pathway regulating that transition between sleep and wakefulness. For the first time, this study has elucidated this process in great biophysical detail.
Researchers focused on a specific area of the brain, which is the suprachiasmatic nucleus (SCN) located in the hypothalamus. This is where the body’s internal clock resides, and it is responsible for determining when we go to sleep, how long we stay asleep, and when we are to wake up. Dr. Andrea Meredith, PhD, the Associate Professor of Physiology at UM SOM, focused heavily on certain ion channels within the SCN. These are proteins that make electrical currents and relay information between neurons. The group of channels that she focused on was the BK potassium channels. These were most active in the SCN region.
The paper on this research recently appeared in Nature Communications, and noted that Dr. Meredith first examined mice, which happen to have the opposite schedule to humans, sleeping during the day rather than at night. In the mice, the BK channels were much more active upon waking. Throughout the day when they were sleeping, these same channels were inactive. Dr. Meredith discovered that the role of the BK channels inactivity during the day was to inhibit wakefulness.
There were two sets of mice examined in this research. There were normal mice and mice whose BK channels were altered so they could not be inactivated. Channel activity was recorded in both through electrodes that were placed on the neurons in the SCN region. The mice whose BK channels were altered had lower levels of neuronal activity, thereby resulting in more daytime wakefulness, which was not a good sign since mice are supposed to sleep during the day.
These findings are somewhat surprising for several reasons. There are no known physiological processes that rely solely on inactive BK channels. The researchers did know that the channels acted in this way; however, they did not understand how neurons used the channel mechanism to regulate the coding of information within this part of the brain. This study is the first to show that the inactivation of BK channels is necessary for regulating the circadian rhythm.
The BK channels are known to help with the regulation of other physiologic functions, such as activating muscles and controlling heart rate, blood pressure, and bladder function. They have also been known to regulate neuronal excitability and help with memory, learning, and motor control. The BK channels in the brain are linked to seizures, addiction, tremors, and difficulty with memory and learning.
Now, with this new research, Dr. Meredith believes they have strong evidence to support the theory that BK channels are specifically involved in the circadian rhythm.
Additionally, researchers in the past believed that the sleep-wake cycle (day-night pattern) of neuronal firing was guided by a completely different mechanism. They believed that it was due to the number of ion channels on the surface of neurons in the SCN region. This new research shows that this is far too simplistic a theory. It is not in the number of channels that exist, but that they are being activated and then inactivated at specific times.
There are clinical implications to these new findings. The inactivation mechanism could be used to create medications that target the sleep-wake cycle. These drugs could treat many sleep disorders, seasonal affective disorder, and even jet lag, which all involve issues within the SCN clock.
Rachael Herman is a professional writer with an extensive background in medical writing, research, and language development. Her hobbies include hiking in the Rockies, cooking, and reading.
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