Image: Wikipedia The body has no way to detect the absence of oxygen and feelings of suffocation are triggered instead by high levels of carbon dioxide. The ‘false-suffocation-alarm theory’ proposes that this alarm is triggered inappropriately in patients with panic disorder but, although several studies have linked high carbon dioxide levels with panic attacks in susceptible individuals, the reasons for this have not been clear. Researchers at the University of Iowa have now shown that inhaled carbon dioxide increases acidity in the brain and evokes fear by activating an acid-sensing ion channel (ASIC1a) in the amygdala. The amygdala plays a key role in the processing and memory of emotional reactions, including fear, but it was not known whether it also directly senses fear-evoking stimuli. ASICs are activated in vitro when extracellular pH falls, and although acidic pH modifies the activity of many receptors and proteins, few others are activated by extracellular acidosis, and few are as exquisitely pH sensitive as ASICs.
In tests in mice, increased carbon dioxide levels led to exaggerated innate and learned fear responses which could be blunted either by disrupting the ASIC1a gene or by pharmacological inhibition of ASIC1a using either the tarantula toxin, psalmotoxin, or A-317567.
The finding that ASIC1a channels in the amygdala act as chemosensors provides a molecular mechanism by which carbon dioxide can trigger fear and anxiety and suggests that targeting brain pH or ASIC channels could lead to new therapies for panic and anxiety disorders.
The study is published in the journal Cell.