2021 Nobel Prize in Physiology: Newly Discovered Temp. and Touch Receptors

The ability to recognize heat, cold, and touch, plays a crucial role in how we interact with the world around us. But how do the nerve signals in our bodies allow us to perceive senses like temperature and touch? This longstanding question has been answered by this year’s Nobel Prize winners.

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How do we perceive and adapt to the world around us? This complex, age-old question ignited the curiosity of many and led to findings that rationalized the inner workings underlying our senses.

Throughout the centuries, scientists have demonstrated that nerve cells are specialized in detecting and transducing distinct stimuli, allowing for the nuanced perception of our environment--for instance, our ability to discern different textured surfaces through our fingertips or to distinguish between pleasant and painful heat. But humanity’s understanding of how the nervous system, sensed temperature and touch stimuli through its electrical impulses had yet to be answered. This year’s Nobel Prize laureates in Physiology or Medicine, David Julius and Ardem Patapoutian, solved this longstanding enigma through their independent discoveries that divulged the mechanisms of sensing heat, cold, touch, and bodily movements.

David Julius, a professor of physiology at the University of California, San Francisco, has dedicated his career to studying how the nervous system senses pain and how chemicals like capsaicin--the compound that gives chili peppers their heat--activates pain receptors. Capsaicin was already well known to stimulate nerve cells and cause pain sensations, but how it actually exerted this function remained a mystery. Julius and his colleagues unearthed how cell-membrane proteins called transient receptor potential (TRP) channels are involved in the perception of pain and temperature, as well as their role in inflammation and pain hypersensitivity.

His team created a library of millions of DNA fragments corresponding to genes expressed in sensory neurons that can react to pain, heat, and touch. They hypothesized that this collection would include a DNA fragment that encoded the protein that was capable of reacting to capsaicin. By expressing each gene in cultured cells that do not usually react to capsaicin, they were eventually able to identify a single gene that could make capsaicin-sensitive cells. Further experiments revealed that this gene, later named TRPV1, encoded an ion channel protein that is activated by heat and inflammatory chemicals. The discovery of TRPV1 was a major breakthrough leading the way to uncover other temperature-sensing receptors and allowing us to comprehend how differences in temperature can induce electrical signals in the nervous system.

Figure 1. Julius used capsaicin from chili peppers to identify TRPV1, an ion channel activated by painful heat and inflammation. Additional related ion channels were also identified and have helped us comprehend how temperature produces electric signals in the nervous system.

While the mechanisms for temperature sensation were being disclosed, Ardem Patapoutian of Scripps Research in La Jolla, California, was working on establishing the unknown receptors activated by mechanical stimuli and how they could convert into our senses of touch and pressure.

Patapoutian and his colleagues identified pressure-sensitive ion channels named Piezo1 and Peizo2--specialized protein molecules embedded in several cell membranes that sent signals in response to touch or pressure. To find these receptors, the researchers first identified a cell line that gave off measurable electric signals when individual cells were poked with a micropipette, and from there, distinguished 72 possible receptors. Pataputian and his collaborators then methodically deactivated the genes, one by one, in pressure-sensitive cells until they found the ones that gave the cells instructions to make these ion channels, thus turning off the cells’ ability to respond to touch. They then inserted those genes into cells that were insensitive to touch and showed that the cells gained this sensitivity. Following the detection of Piezo1 and Piezo2, further work has uncovered that these ion channels play a key role in proprioception (the ability to sense one’s body position and motion in space) and regulate important physiological processes including blood pressure, respiration, and urinary bladder control.

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Figure 2. Using cultured mechanosensitive cells, Patapoutian identified ion channels Piezo1 and Piezo2, which are activated by mechanical force.

The seminal discoveries of TRPV1 and Piezo channels have enabled us to understand how temperature and touch can initiate nerve impulses that allow us to sense our environment. The TRP channels are significant for our ability to perceive heat and cold. The Piezo channels provide us with the sense of touch and proprioception. Furthermore, these proteins also contribute to myriad physiological processes that depend on sensing temperature and touch stimuli. This newfound knowledge is being utilized to develop treatments for chronic pain and touch or internal organ sensing disorders.

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Figure 3. The breakthroughs of TRPV1 and Piezo explain how heat, cold, and touch can initiate signals in our nervous system. The identified ion channels are important for many physiological processes and disease conditions.

Sources

Lewis, Tanya. “2021 Medicine Nobel Prize Winner Explains the Importance of Sensing Touch.” Scientific American, Scientific American, 8 Oct. 2021, www.scientificamerican.com/article/2021-medicine-nobel-prize-winner-explains-the-importance-of-sensing-touch/.

Lewis, Tanya. “What Chili Peppers Can Teach Us About Pain.” Scientific American, Scientific American, 5 Sept. 2019, www.scientificamerican.com/article/what-chili-peppers-can-teach-us-about-pain/.

Mueller, Benjamin, et al. “Nobel Prize Awarded for Research about Temperature and Touch.” The New York Times, The New York Times, 4 Oct. 2021, www.nytimes.com/2021/10/04/health/nobel-prize-medicine-physiology-temperature-touch.html.

“Press Release: The Nobel Prize in Physiology or Medicine 2021.” NobelPrize.org, 2021, www.nobelprize.org/prizes/medicine/2021/press-release/.

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