October 26, 2000
Researchers Discover Molecule That Detects Touch
Researchers have identified a protein that may play an important
role in sensing delicate touch. According to the scientists, their
finding may offer new avenues for investigating the molecular basis of
touch.
In an article published in the October 26, 2000, issue of the
journal Nature, a research team that included Howard Hughes
Medical Institute investigator Michael J. Welsh reported
that knocking out the gene BNC1 in mice greatly reduces the
ability to sense light touch. Deleting the gene impairs the function of
receptors that surround the hair follicles on the animal's skin. When a
hair is touched, receptors near the hair fire, triggering a nerve
impulse that signals that the hair has been moved.
“Although there has been excellent anatomical and physiological work on the sense of touch, the molecules that actually detect touch have remained elusive.”
Michael J. Welsh
"Although there has been excellent anatomical and physiological work
on the sense of touch, the molecules that actually detect touch have
remained elusive," said Welsh, who is at the University of Iowa School
of Medicine. According to Welsh, the sense of touch is not as well
understood at the molecular level as the senses of vision and smell
primarily because it is difficult to study the tiny nerve endings that
sense touch.
Nevertheless, scientists had long suspected that mechanical touch
stimuli are translated into nerve impulses when ion channels are opened
in response to touch. The opening of these channels, which are pores in
the membranes of nerve cells, allows sodium to flood in, launching a
nerve impulse. "The hypothesis that an ion channel is involved was
based on the fact that a touch response is much faster than could be
attributed to the types of slower chemical receptors that underlie
vision or smell," said Welsh.
The scientists concentrated their studies on the sodium ion channel
protein BNC1 because it was a mammalian member of a sodium channel
family that had been implicated in touch sensing in the roundworm,
C. elegans. BNC1's similarity to the worm channel led the
scientists to test its involvement in touch. They found that BNC1
contributed to one form of touch, called rapidly-adapting light
touch.
"Light touch allows you to detect, for example, a mosquito landing
on your arm," said Welsh. "However, while this touch sense is
sensitive, it does not persist. In the case of the mosquito, if you
look away and the mosquito does not move or bite, you can no longer
feel it." By contrast, said Welsh, mammals have other nerves that can
detect heavier and more persistent touch sensation.
To investigate BNC1's function in mice, Welsh and his colleagues
knocked out the gene for BNC1 and tested whether the skin of the mice
showed normal detection of light touch. Gary R. Lewin and colleagues at
the Max-Delbrück-Center for Molecular Medicine in Germany used a
small computer-controlled probe to touch a patch of skin on the
knockout mouse. This experimental approach enabled Lewin and his
colleagues to record the level of electrical nerve impulse triggered by
various levels of hair deflection. Lewin and Margaret P. Price of
Welsh's laboratory were co-lead authors of the Nature
article.
Tests of skin patches from normal and knockout mice revealed that
the knockout mice had greatly reduced touch sensitivity when compared
to normal mice. Touch sensation in the knockout mice was diminished,
but it did not disappear entirely. "We postulate that the BNC1 channel
may be one component of a larger receptor complex," he said. "In the
absence of BNC1, other components of the channel may retain sufficient
function for some residual sense of light touch."
Welsh and his colleagues also showed that BNC1 protein surrounds
hair follicles, as would be expected for a protein involved in sensing
touch. "We found the protein located in fibers that surround the hair
shaft like a picket fence," said Welsh. "So, when a shaft of hair bends
in any direction, these fibers are deflected."
BNC1 may also be involved in detecting pain, so the scientists
explored whether neurons involved in pain-sensing functioned normally
in the BNC1-knockout mice. "Those nerve cells seemed normal,"
said Welsh. "And although it's difficult to exclude the possibility
that BNC1 is involved in pain perception, we could find no evidence for
that involvement." Welsh emphasized that the discovery of BNC1's role
opens a promising research pathway for understanding touch.
"I think this is an important first step toward understanding this
elusive sense of touch," he said. "Now, we need to look at other
members of this family of ion channel proteins, as well as the proteins
that associate with these channels," Welsh said. Studies of BNC1 and
related proteins may also aid in understanding the stretch-sensing
mechanisms in blood vessels and the heart that signal the brain to
control blood pressure, Welsh noted.
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