These windpipe cells trigger coughs to keep water out of the lungs

Experiments in mice show that neuroendocrine cells in the trachea react to water and acid

Neuroendocrine cells (green) are scattered across the trachea and larynx, as imaged in a mouse. A new study reveals how these cells communicate with cells in the nervous system (pink) to help prevent substances such as water or acid from getting into the lungs.

Laura Seeholzer

By Nora Bradford

April 18, 2024 at 2:00 pm

Have you ever taken a gulp of water that goes down the wrong way? Or felt acid reflux bubbling up? It feels like your windpipe seizes up and you quickly emit a cough or maybe three.

Researchers now know which cells are responsible for that quick reaction. Neuroendocrine cells in the larynx and trachea, which make up the passageway from the mouth to the lungs, can sense water and acid passing through, a team reports in the April 19 Science. Those cells then communicate with the nervous system to trigger reflexes, like coughing.

“This is not at all what I was expecting [these cells] to be detecting or doing.” says Laura Seeholzer, a neurophysiologist at University of California, San Francisco.

Neuroendocrine cells typically release hormones throughout the body. One place they hang out is in the larynx and trachea, which among other things, “are gatekeepers for the airways,” Seeholzer says. “If you have water or acid or any other stimuli that enter into your airways, it can cause damage which then can lead to your inability to breathe.”

Until recently, scientists had little idea about what information these upper airway–based neuroendocrine cells collected and whether they communicated with the nervous system.

Bright green dots are scattered throughout pink stringlike strands that are vertical in this image. The green dots are neuroendocrine cells from a mouse airway and the pink is part of the nervous system. — This close-up of cells in the upper airway of a mouse shows neuroendocrine cells (green) in the trachea and larynx, which send signals to the nervous system (pink) when an unwanted stimulus arrives, triggering a cough or similar reflexes to protect the lungs.Laura Seeholzer

In experiments with mouse cells in dishes, Seeholzer and UCSF physiologist David Julius tracked the cells’ calcium levels, an indicator of how chatty the cells are with neighboring cells, to see what stimuli caused them to become active. Unlike neuroendocrine cells in the lungs which respond to pressure changes those in the larynx and trachea responded to water and acid. Activating these cells in the mice triggered swallowing and coughing, presumably to help expel unwelcome substances that ended up in the airway.

“It turns out that there’s a lot of cells that act as basically sensory detectors and then they communicate with the nervous system in order to drive behavior,” Seeholzer says. Like taste buds or outer skin cells, neuroendocrine cells in your airways help and protect you from harmful substances.