The Response to High CO(2) Levels Requires the Neuropeptide Secretion Component HID-1 to Promote Pumping Inhibition

Carbon dioxide (CO(2)) is a key molecule in many biological processes; however, mechanisms by which organisms sense and respond to high CO(2) levels remain largely unknown. Here we report that acute CO(2) exposure leads to a rapid cessation in the contraction of the pharynx muscles in Caenorhabditis elegans. To uncover the molecular mechanisms underlying this response, we performed a forward genetic screen and found that hid-1, a key component in neuropeptide signaling, regulates this inhibition in muscle contraction. Surprisingly, we found that this hid-1-mediated pathway is independent of any previously known pathways controlling CO(2) avoidance and oxygen sensing. In addition, animals with mutations in unc-31 and egl-21 (neuropeptide secretion and maturation components) show impaired inhibition of muscle contraction following acute exposure to high CO(2) levels, in further support of our findings. Interestingly, the observed response in the pharynx muscle requires the BAG neurons, which also mediate CO(2) avoidance. This novel hid-1-mediated pathway sheds new light on the physiological effects of high CO(2) levels on animals at the organism-wide level.