People with DFNA2 Hearing Loss Show Increased Touch Sensitivity

The
members of the Spanish and Dutch families who participated in the study were
quite amazed when the researchers from Berlin
unpacked their testing equipment. Many of the family members suffer from
hereditary DFNA2 hearing loss, but the researchers were less interested in
their hearing ability than in their sense of touch. The hearing impairment is
caused by a mutation which disrupts the function of many hair cells in the
inner ear. This mutation, the researchers suspected, might also affect the
sense of touch.

Tiny,
delicate hairs in our inner ear vibrate to the pressure of the sound waves. The
vibrations cause an influx of positively charged potassium ions into the hair
cells. This electric current produces a nerve signal that is transmitted to the
brain – we hear. The potassium ions flow through a channel in the cell membrane
and again out of the hair cells. This potassium channel, a protein molecule
called KCNQ4, is destroyed by the mutation in hearing-impaired people. The
sensory cells gradually die off due to overload. "But we have found that
KCNQ4 is present not only in the ear, but also in some sensory cells of the
skin,” Thomas Jentsch explained. “This gave us the idea that the mutation might
also affect the sense of touch. And this is exactly what we were able to show
in our research, which we conducted in a close collaboration with the lab of
Gary Lewin, a colleague from the MDC who is specialized in touch sensation.”

Whether we
caress our child, search in our bag for a certain object or hold a pen in our
hand – each touch conveys a variety of precise and important information about
our environment. We distinguish between a rough and smooth surface by the
vibrations that occur in the skin when the surface is stroked. For the
different touch stimuli there are sensory cells in the skin with different
structures – through the deformation of the delicate structures, electric nerve
signals are generated. Exactly how this happens is still a mystery – of the
five senses of Aristoteles, the sense of touch is the least understood.

Clearly
there are parallels to hearing, as the findings of Matthias Heidenreich and
Stefan Lechner from the research groups of Thomas Jentsch and Gary Lewin show.
As a first step, the researchers in the Jentsch lab created a mouse model for
deafness by generating a mouse line that carries the same mutation in the
potassium channel as a patient with this form of genetic hearing loss. The
touch receptors in the skin where the KCNQ4 potassium channel is found did not
die off due to the defective channel like they did in the ear, but instead
showed an altered electric response to the mechanical stimuli in the mutated
mouse. They reacted much more sensitively to vibration stimuli in the low
frequency range. The outlet valve for potassium ions normally functions here as
a filter to dampen the excitability of the cells preferentially at low
frequencies. This normally tunes these mechanoreceptors to moderately high
frequencies in normal people. In mice lacking functional KCNQ4 channels, these
receptors can no longer distinguish between low and high frequencies.

The deaf
patients with mutations in the potassium channel who were examined by Stefan
Lechner and Matthias Heidenreich showed exactly the same effect. They could
even perceive very slow vibrations that their healthy siblings could not
perceive. Due to mutations in the KCNQ4 channel gene, the fine tuning of the
mechanoreceptors for normal touch sensation was altered.

The
sensation of touch varies greatly from person to person – some people are much
more sensitive to touch than others. DFNA2 patients are extremely sensitive to
vibrations, according to Gary Lewin and Thomas Jentsch. “The skin has several
different types of mechanoreceptors, which respond to different qualities of
stimuli, especially to different frequency ranges. The interaction of different
receptor classes is important for the touch sensation. Although the receptors
we studied became more sensitive due to the loss of the potassium channel, this
may be outweighed by the disadvantage of the wrong ‘tuning to other
frequencies’. With KCNQ4 we have for the first time identified a human gene
that changes the traits of the touch sensation.”

The
research group led by Thomas Jentsch belongs both to the FMP and the MDC in
Berlin and studies ion transport and its role in disease. The group led by Gary
Lewin belongs to the MDC and is specialized in peripheral sensory perception.

KCNQ4 channel (red) at skin mechanosensory nerve endings (green) (Graphic: M. Heidenreich/Copyright: FMP, MDC)

Contact:
Professor
Thomas J. Jentsch
FMP
(Leibniz-Institut für Molekulare Pharmakologie) and MDC (Max Delbrück Center
for Molecular Medicine); Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone:
0049-30-9406-2961 e-mail: Jentsch@fmp-berlin.de
http://www.fmp-berlin.de/jentsch.html
Professor
Gary R. Lewin
Molecular
Physiology of Somatic Sensation Department of Neuroscience MDC (Max Delbrück
Center for Molecular Medicine); Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone:
0049-30-9406-2430, e-mail: glewin@mdc-berlin.de
http://www.mdc-berlin.de/en/research/research_teams/molecular_physiology_of_somatic_sensation/index.html