Cough! What happens when something goes down the wrong way

Certain cells in a mouse’s trachea react to water and acid, triggering coughs

This image of a mouse trachea and larynx on a black background reveals a constelletion of small green dots scattered througout it. The green dots are neuroendocrine cells. Areas around the edges of the image that appear pink are part of the nervous system.

Neuroendocrine cells (green) dot this mouse trachea and larynx. A new study reveals how these cells communicate with those in the nervous system (pink) to help keep substances such as water or acid from getting into the lungs.

Laura Seeholzer

Have you ever taken a gulp of water that goes down the wrong way? Or felt acid reflux bubbling up? You probably emitted a cough or three.

For a long time, scientists didn’t know exactly what caused this. But they knew this quick reaction was important. Water or something else that doesn’t belong in the airway “can cause damage,” explains Laura Seeholzer. She’s a neurophysiologist at the University of California, San Francisco (UCSF). That damage could even halt our breathing.

Seeholzer and a UCSF coworker recently found that certain cells help protect against this. These neuroendocrine (Ner-oh-EN-do-krin) cells can sense water or acid passing through the the larynx and trachea. This passageway runs between the mouth and lungs. Neuroendocrine cells here communicate with the nervous system. That triggers reflexes such as coughing.

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. When an unwanted stimulus arrives, these cells send signals to the nervous system (pink). Those signals trigger a cough or similar reflexes to protect the lungs.Laura Seeholzer

The researchers shared their finding April 19 in Science.

“This is not at all what I was expecting [these cells] to be detecting or doing,” Seeholzer says. Neuroendocrine cells usually release hormones that move throughout the body. One place where these cells hang out is the larynx and trachea. But scientists had little idea what information neuroendocrine cells collected here. They also didn’t know whether the cells talked to the nervous system.

Seeholzer and physiologist David Julius grew neuroendocrine cells from mouse airways in a dish. They wanted to see what stimuli caused the cells to become active. To do this, they tracked calcium levels in the cells. These levels point to how much the cells are chatting with their neighbors. The cells responded to water and acid, they found.

Other experiments activated these cells in mice. The neuroendocrine cells made the mice swallow and cough. This may help kick unwelcome substances out of the airway.

A different trigger activates neuroendocrine cells in the lungs. Those cells respond to pressure changes.

“It turns out that there’s a lot of cells that act as basically sensory detectors,” Seeholzer says. “And then they communicate with the nervous system in order to drive behavior.” Other sensors include taste buds and outer skin cells. Together, they help protect us from harmful substances.

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