Scientists Uncover the Protein Responsible for Cold Sensation

Researchers from the University of Michigan have identified the protein that enables mammals to sense cold temperatures, filling a long-standing knowledge gap in the field of sensory biology. The findings, published in Nature Neuroscience, could help scientists better understand how we sense and suffer from cold temperatures during the winter months and why some patients experience cold differently under certain disease conditions.

“The field started uncovering these temperature sensors over 20 years ago, with the discovery of a heat-sensing protein called TRPV1,” said neuroscientist Shawn Xu, a professor at the U-M Life Sciences Institute and a senior author of the new research. “Various studies have found the proteins that sense hot, warm, even cool temperatures—but we’ve been unable to confirm what senses temperatures below about 60 degrees Fahrenheit.”

Building upon their previous work with millimeter-long worms called Caenorhabditis elegans, the researchers tested their hypothesis in mice that were missing the gene for a protein called GluK2 (short for Glutamate ionotropic receptor kainate type subunit 2). Through a series of experiments, the team found that the mice responded normally to hot, warm, and cool temperatures but showed no response to noxious cold.

GluK2 is primarily found on neurons in the brain, where it receives chemical signals to facilitate communication between neurons. However, it is also expressed in sensory neurons in the peripheral nervous system (outside the brain and spinal cord). “We now know that this protein serves a totally different function in the peripheral nervous system, processing temperature cues instead of chemical signals to sense cold,” said Bo Duan, U-M associate professor of molecular, cellular, and developmental biology and co-senior author of the study.

Professor Xu believes that this discovery could have implications for human health and well-being, particularly for cancer patients receiving chemotherapy who often experience painful reactions to cold. “This discovery of GluK2 as a cold sensor in mammals opens new paths to better understand why humans experience painful reactions to cold, and even perhaps offers a potential therapeutic target for treating that pain in patients whose cold sensation is overstimulated,” Xu said.

The research was supported by the National Institutes of Health, and all procedures performed in mice were approved by the Institutional Animal Care and Use Committee and performed in accordance with the institutional guidelines.

Study: The kainite receptor GluK2 mediates cold sensing in mice (DOI: 10.1038/s41593-024-01585-8) 

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