The tight embrace of welcoming hugs, the cozy warmth of a crackling fireplace, the brisk chill of afternoon walks in snowy woods—these are some of the feelings that, for me, make the winter holidays one of the best times of the year. This season, I’m also choosing to be thankful for the biology that makes these sensations possible.
This year’s Nobel Prize in Physiology and Medicine went to two scientists who discovered the receptors that allow us to sense touch and temperature. Joining other sensory mechanisms recognized by the Nobel committee, these discoveries add to our knowledge of how we interact with the world around us.
Feeling the Heat (and Cold)
A not so nice, yet inevitable, part of my holidays happens when I carelessly grab a roasting pan or cookie tray that came out of the oven only minutes earlier. The flash of pain reminding me that I forgot to use an oven mitt stems from a sensory neuron ion channel called TRPV1. This channel is normally closed but opens when exposed to hot temperatures, allowing that heat to be registered as pain.
The identification of TRPV1 as part of the “pain pathway” was discovered by David Julius, one of the recipients of this year’s Nobel Prize in Physiology and Medicine. The discovery, which was first reported in 1997, identified the first of a series of ion channels that are now known to respond to a whole range of temperatures.
In the initial discovery of TRPV1, the research team created a cDNA library of genes expressed in neuronal cells that react to the presence of capsaicin. Capsaicin is the chemical responsible for peppers’ spicy heat. They then transfected capsaicin-unresponsive cells with the cDNA clones and exposed the transfected cells to capsaicin. In most cases, capsaicin elicited no response from the cells. However, when cells containing the gene for TRPV1 were exposed to capsaicin, the researchers observed a change: an influx of calcium ions into the cells.
A similar response happened when the cells expressing TRPV1 experienced hot temperatures, not just a “hot” chemical. Later work showed that these responses are responsible for sensing the burning pain of a spicy pepper or of a hot cooking pan. Since the 1997 report, other temperature-responsive ion channels have been discovered, including TRPM8, an ion channel that allows neurons to sense cold temperatures.
Where TRPV1 and TRPM8 allow us to experience heat and cold, Piezo ion channels let us sense touch. Named after the Greek word for pressure, the Piezo1 and Piezo2 ion channels were first reported in 2010 by Ardem Patapoutian, the second recipient of this year’s Nobel Prize in Physiology and Medicine.
In addition to letting us feel the tight squeeze of a loved one’s hug during a holiday gathering (or of a waistband that’s grown too tight after a festive meal!), the Piezo channels help us sense our body’s motion and position. Studies also show that the Piezo channels regulate other bodily functions, like blood pressure.
To discover the Piezo1 and Piezo2 ion channels, Patapoutian and his research team used neuronal cells that, when poked, released a small jolt of electricity—a measurable response to touch. One-by-one, they inactivated various genes, looking for proteins that, when missing, made the cells indifferent to the researchers’ pokes and prods. From that work, Piezo1 and Piezo2 were discovered. These Piezo proteins are transmembrane ion channels that open when a cell membrane experiences mechanical force.
Sensing Our World
The joy I feel when receiving a hug from a loved one doesn’t depend on me knowing anything about Piezo ion channels: the mechanism of how my neurons respond to mechanical pressure is, frankly, not something I will have to think about often.
But what I admire about Patapoutian’s and Julius’s discoveries is the connection they forge between complex biology and human experience. It’s research that gives us a small glimpse into the details that help us enjoy the world and enjoy one another.