Sleep apnea is a dangerous sleep disorder in which breathing stops and resumes repeatedly during sleep.
According to recent mouse studies, the target is an ion channel already shown to affect blood pressure in obese mice.
Recent studies using obese mice suggest that specialized channel proteins are potential therapeutic targets for sleep apnea and other abnormally slow breathing disorders in obese people, according to scientists at Johns Hopkins Medicine. Add proof that there is.
A cation channel known as TRPM7, this protein is located in the body of the carotid artery, tiny sensory organs in the neck that sense changes in oxygen and carbon dioxide levels, as well as certain hormones such as leptin in the bloodstream. doing. The TRPM7 protein helps transport and regulate positively charged molecules into and out of cells in the carotid body.
Dr. Renis Kim, Postdoctoral Fellow johns hopkins medicine The current study is the leader and extends previous results from the lab that showed that TRPM7 plays a role in the development of hypertension in mice.
A recent study detailed in a recently published study journal of physiologydemonstrated that TRPM7 is involved in respiratory depression in obese mice exhibiting symptoms of sleep-disordered breathing.
Up to 45% of obese Americans are believed to suffer from sleep-disordered breathing. If untreated, the condition can worsen the course of heart disease and diabetes, cause severe fatigue, and even die from lack of oxygen. Although helpful in relieving apnea, CPAP therapy is often poorly tolerated by patients.
“CPAP actually works for most patients, but most patients are not adhering to this regimen,” says Kim. “Having learned that TRPM7 contributes to hypertension and sleep-disordered breathing, we wondered if blocking or eliminating that channel could provide a new therapeutic target.”
Using silencing[{” attribute=””>RNA, the researchers knocked out the gene responsible for the production of the TRPM7 channel protein, reducing the number of TRPM7 channels in the carotid bodies of obese mice. Mice then underwent a sleep study, during which researchers observed their breathing patterns and blood oxygen levels.
In obese mice with blocked TRPM7, the researchers noted large differences in their rates of minute ventilation, or the amount of air inhaled and exhaled by the lungs per minute. The obese mice showed a 14% increase in their minute ventilation, 0.83 milliliters of air per minute (mL/min/g) during sleep. Researchers say these data are a significant improvement in ventilation when compared to obese mice that had TRPM7, whose average minute ventilation was 0.73 mL/min/g. These findings indicate the ventilatory capacity in these mice was improved while they slept, effectively combating the decreased breathing patterns of sleep apnea.
Notably, the researchers found that despite the increased ventilation in obese mice lacking TRPM7, their blood oxygen levels did not increase. For this finding, researchers exposed the mice to hypoxic — or low-oxygen — environments and then monitored their breathing patterns. Although the mice’s minute ventilation increased by 20%, from 1.5 mL/min/g to 1.8 mL/min/g, their bloodstream oxygen levels decreased, meaning their additional inhalations did not help saturate the body with more oxygen.
“This suggests that treatments designed to reduce or erase TRPM7 in carotid bodies would not be workable for people living in low-oxygen environments, such as those in very high altitudes, or for those with conditions that already limit blood oxygen saturation, such as lung disease,” says Kim.
The team’s findings also illustrate that the hormone leptin — which is produced in fat cells and is responsible for curbing appetite — may cause an increase in TRPM7 channels. Leptin is already known to accelerate production and increase the concentration of TRPM7 in carotid bodies. In obese mice who possess more fat cells, the increased amount of leptin may lead to an oversaturation of TRPM7. These high levels of the cation channel in turn may lead to the low respiration rates observed in obese mice with TRPM7.
“We have shown that the genetic knockdown of TRPM7 in carotid bodies reduces suppressed respiration in sleep-disordered breathing,” says Vsevolod (Seva) Polotsky, M.D., Ph.D., director of sleep research and professor of medicine at the Johns Hopkins University School of Medicine. “While more research is needed, carotid body TRPM7 is a promising therapeutic target not only for hypertension in obesity but also for abnormal breathing during sleep associated with obesity.”
Reference: “TRPM7 channels regulate breathing during sleep in obesity by acting peripherally in the carotid bodies” by Lenise J. Kim, Mi-Kyung Shin, Huy Pho, Wan-Yee Tang, Nishitha Hosamane, Frederick Anokye-Danso, Rexford S. Ahima, James S. K. Sham, Luu V. Pham and Vsevolod Y. Polotsky, 10 October 2022, The Journal of Physiology.
DOI: 10.1113/JP283678
The study was funded by the National Heart, Lung, and Blood Institute, the American Academy of Sleep Medicine Foundation, the American Thoracic Society, and the American Heart Association (AHA).
The authors of this study report no conflict of interest.
