The
winter sun feels welcome, but not so a summer sunburn. Research over
the past 20 years has shown that proteins on the surface of nerve cells
enable the body to sense several different temperatures. Now scientists
have discovered how just a few of these proteins, called ion channels,
distinguish perhaps dozens of discrete temperatures, from mildly warm to
very hot.
Researchers
showed that the building blocks, or subunits, of heat-sensitive ion
channels can assemble in many different combinations, yielding new types
of channels, each capable of detecting a different temperature. The
discovery, in cell cultures, demonstrates for the first time that only
four genes, each encoding one subunit type, can generate dozens of
different heat-sensitive channels.
“Researchers
in the past have assumed that because there are only four genes, there
are only four heat-sensitive channels, but now we have shown that there
are many more,” said Jie Zheng, leader of the research and an associate
professor of physiology and membrane biology at the
The research publishes in the Journal of Biological Chemistry on March 2.
Ion
channels are pores in cell membranes. Their ability to open and close
controls the flow of charged ions, which turns neuron signalling on or
off—in this case to inform the body of the temperature the neuron
senses.
The
researchers found that when different subunits combine, the resultant
hybrid, or heteromeric, channel can detect temperatures about midway
between what the “parent” channels detect.
One
of the channels they studied, called TRPV1, reacts to hot
temperatures—about 100 F. It is also responsible for the ability to
sense spicy foods, such as chili peppers. A second channel, TRPV3,
responds to temperatures of about 85 F. It also senses many food flavors
such as those found in rosemary, oregano, vanilla and cinnamon that
elicit a warm sensation.
When
the TRPV1 and TRPV3 subunits recombine, the heteromeric channel is
tuned to about 92 F. Surprisingly, the study showed that the hybrid
channel has an even higher chemical sensitivity than the channels that
made it up.
Zheng
and his colleagues also showed that channels made up of TRPV1 and TRPV3
subunits react to heat at a rate about midway between that of the two
constituent channel subunits. But repeatedly exposing the hybrid
channels to their target temperature boosted their response, a behavior
called sensitization, which TRPV3 also exhibits.
“It
says ‘I remember this temperature. I will make a really loud noise to
tell the system that it is coming,'” Zheng said. The process allows the
body to be more sensitive to temperature.
By
contrast, TRPV1 typically responds the same way when repeatedly exposed
to its target temperature — and sometimes even decreases its response,
a process called desensitization. It helps the body to adapt to high
temperature, Zheng explained.
The
research builds on work the team published in 2007 demonstrating that
the heat-sensitive subunits can combine to form heteromeric channels.
However, at the time, scientists didn’t know how these channels respond
to heat. The new work shows that the channels are indeed sensitive to
different temperatures.
“Knowing
that there are many distinct heat-sensing ion channels now opens the
way to understand how neurons encode precise temperature information, an
important process that allows us to enjoy the rich spectrum of
temperature in life—a memorable warm handshake, a soothing shower and a
cup of hot latte—and add vanilla flavor, please,” Zheng said. “It also
may provide insights regarding the causes and potential treatments for
temperature-sensitivity disorders, such as Raynaud’s syndrome.”
Raynaud’s
syndrome is a condition that causes some areas of the body—such as
fingers, toes, the tip of the nose and ears—to feel numb and cool in
response to cold temperatures or stress. The cause is unknown.
The
scientists introduced the genes for TRPV1 and TRPV3 channel subunits to
cultured human kidney cells. They tagged the genes with fluorescent
markers to confirm when the resulting proteins had combined to form a
new channel complex.
Once
functional channels were formed, the researchers used a glass pipette
with a very fine tip to record ion channels’ responses to temperature
changes.
In
order to rapidly increase the temperature, they built an apparatus that
allowed them to deliver an infrared laser beam to the cell. The method
allowed them to heat the channel more than a thousand times faster than
commercially available heating devices.
The
collaborative research is funded by the National Institutes of Health,
the American Heart Association and the Chinese government.
