Breathing is both the first and last act of life. Although our respiratory system is remarkably robust, several potentially fatal situations can depress or halt ventilation—known as apnoea. These include the therapeutic use of opioids for pain relief, the illicit use of opioids like fentanyl (which resists naloxone, an opioid receptor blocker), respiratory conditions such as sleep apnoea, and viral infections like COVID-19. In response to these challenges, they identified a fundamental mechanism through which sensory input from peripheral chemoreceptors in the carotid body modulates and powerfully drives breathing.
The carotid body plays a critical role in protecting against hypoxia by triggering a strong increase in ventilation. While we know that hypoxia activates the carotid body, researchers have yet to fully understand the molecular and cellular mechanisms that determine its sensitivity—how much ventilation increases in proportion to the severity of hypoxia. These mechanisms are vital for maintaining respiratory balance and hold considerable clinical importance. The team recently discovered a novel, interactive mechanism in the carotid body involving glutamate as an ‘accelerator’ and gamma aminobutyric acid (GABA) as a ‘brake’ in regulating respiratory drive.
For the first time, the team revealed a modifiable mechanism that fundamentally stimulates breathing, offering a highly clinically relevant strategy to restore respiratory drive in conditions like sleep apnoea and opioid-induced respiratory depression.