By tweaking a system in the ear that limits how much
sound is heard, a global team of
researchers has discovered one alteration that shows that
the ability of the ear to "turn itself down"
contributes to protecting against permanent hearing loss.
The report was published Jan. 20 in PLoS
"There's some uncertainty in the field about what this
sound-limiting system is used for," said
Paul Fuchs, an author on the paper and professor of
otolaryngology-head and neck surgery and
director of the Center for Sensory Biology
Institute for Basic Biomedical Sciences at Johns
Hopkins. "Now we've definitively shown that this system
functions in part to prevent acoustic trauma."
To get a better handle on this sound-limiting system
in the ear, the research team built on
previous findings in the field and focused its efforts on
the nAChR protein found on so-called sensory
hair cells in the ear. Nerve cells from the brain release
signals that are picked up by nAChR and turn
down these sensory hair cells.
The team genetically altered a single building block
in the nAChR protein and tested mice for
their ability to hear. "This point mutation was designed to
produce a so-called gain of function in which
the inhibitory effect of ACh should be greater than
normal," Fuchs said.
The altered mice were less able to hear soft sounds
than normal mice, showing that the genetic
alteration made in the nAChR protein did indeed further
"turn down" the ear. The team then asked if
the alteration in nAChR — and therefore the improved
sound-blocking ability of these altered mice —
also could protect from sound damage.
The team blasted 100-decibel sound at mice and again
measured their ability to hear. "One
hundred decibels, for me, is painfully loud, and
conversation is impossible," Fuchs said. "But sound
levels in night clubs or rock concerts can be that high,
and extended exposure to sound at that volume
can cause hearing loss."
The researchers found that mice with the altered,
gain-of-function nAChR suffered less
permanent hearing damage compared to normal mice. "We think
this pathway could be a therapeutic
target for protecting from sound damage," Fuchs said. "So
far, there is little or no specific
pharmacology of hearing. We're still learning how the inner
ear works. The encouraging news is that
molecular mechanisms like the hair cell's nAChR frequently
involve unique gene products, so there is a
real chance of finding ear-specific drugs in the
Until then, Fuchs suggests limiting time spent at rock
concerts, and wearing earplugs, to protect
This study was funded by the National Institute of
Deafness and other Communication
Disorders, Howard Hughes Medical Institute, National
Organization for Hearing Research, Tinnitus
Research Initiative, Agencia Nacional de Promocion
Cientifica y Tecnologica of Argentina and
University of Buenos Aires.
Authors on the paper are Fuchs; Julian Taranda, Jimena
Ballestero, Eleonora Katz, Jessica
Savino and A. Belen Elgoyhen, of Instituto de
Investigaciones en Ingenieria Genetica y Biologia
Molecular in Buenos Aires, Argentina; Stephane Maison and
M. Charles Liberman, of Harvard Medical
School; Douglas Vetter, of Tufts University School of
Medicine; and Jim Boulter, of University of
California, Los Angeles.