According to Johns Hopkins Medicine researchers who conducted a study in mice, specialized channel proteins are potential therapeutic targets for sleep apnea and other unusually slow breathing problems in obese humans. The carotid bodies, which are tiny sensory organs in the neck that sense changes in oxygen and carbon dioxide, as well as certain blood-borne hormones like leptin, include the cation channel protein TRPM7. The flow of positively charged molecules into and out of carotid body cells is regulated and transported by TRPM7 proteins.

The current study, conducted at Johns Hopkins Medicine’s Polotsky Research Laboratory and led by postdoctoral researcher Lenise Kim, PhD, expands on the lab’s previous findings that indicated that TRPM7 was involved in the progression of high blood pressure in mice. The most recent research, detailed in a publication first published Oct. 10 in The Journal of Physiology, showed that TRPM7 is involved in the restriction of breathing in obese mice that show symptoms of sleep-disordered breathing.

Up to 45% of obese Americans are thought to suffer from sleep disordered breathing, which is defined by breathing that comes and goes throughout sleep. If left untreated, the disease can exacerbate diabetes and heart disease, lead to severe exhaustion and even lead to death from insufficient oxygenation. Although CPAP therapy is often poorly accepted by patients, lifestyle modifications such as weight loss and regular use of CPAP machines can help treat sleep apnea.

“CPAP actually works for most patients, the fact is most patients don’t adhere to this treatment,” says Kim. “So knowing that TRPM7 contributes to high blood pressure and sleep-disordered breathing, we wondered if blocking or eliminating this channel might offer a new treatment target.” Using silent RNA, the researchers knocked out the gene responsible for producing the TRPM7 channel protein, thereby reducing the number of TRPM7 channels in the carotid bodies of obese mice. The mice then underwent a sleep study, during which the researchers observed their breathing patterns and blood oxygen levels.

The amount of air inhaled and expelled by the lungs per minute was significantly different in obese mice with blocked TRPM7 than in normal mice. Minute ventilation of obese mice increased by 14% during sleep, reaching 0.83 milliliters of air per minute per kilogram (mL/min/g). Compared to obese mice with TRPM7, whose average minute ventilation was 0.73 ml/min/g, the researchers say these data show a dramatic improvement in ventilation. These results demonstrate that the ventilatory capacity of these mice was enhanced during sleep, successfully reversing the reduced breathing patterns associated with sleep apnea.

Notably, the researchers found that even though large mice without TRPM7 had better breathing, their blood oxygen levels remained the same. The mice were placed in hypoxic or low oxygen conditions, and the researchers then observed the breathing patterns of the mice to come to this conclusion. The mice’s blood oxygen levels decreased even though their minute ventilation increased by 20%, from 1.5 ml/min/g to 1.8 ml/min/g, indicating that their larger inhalations n didn’t help saturate the body with more oxygen.

“This suggests that treatments designed to reduce or erase TRPM7 in carotid bodies would not be feasible for people living in low oxygen environments, such as those at very high altitudes, or for those with conditions that already limit blood oxygen saturation, such as lung disease,” Kim says. The research team’s findings also show that leptin, a hormone produced in fat cells and regulating hunger, may cause an increase in TRPM7 channels. Levels and production of TRPM7 are already known to be accelerated by leptin in carotid bodies.

Leptin levels may increase in obese mice because they have more fat cells, which could lead to overstimulation of TRPM7. The decrease in respiration rates observed in obese mice with TRPM7 may, in turn, be the result of these elevated cation channel concentrations. “We have shown that genetic inactivation of TRPM7 in carotid bodies reduces suppressed breathing in sleep-disordered breathing,” says Vsevolod (Seva) Polotsky, MD, Ph.D., director of sleep research and professor of Medicine at Johns Hopkins University. Medicine School. “Although further 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.” (ANI)

(This story has not been edited by the Devdiscourse team and is auto-generated from a syndicated feed.)