functioning P2X 2 receptors experienced a hearing loss of about
18 dB, and this took more than 24 hours to recover.
We could measure this hearing loss by putting calibrated
clicks and brief tones at various frequencies into the left ears of
the mice and then measuring the auditory brainwaves on the
skin around the ear. This revealed a novel slow hearing adap-
tation mechanism, with sustained loud sound causing the
cochlear tissue to release adenosine triphosphate and activate
the P2X 2 receptors. This reduced the ability of the hair cells
to transduce sound broadly throughout the cochlea for much
longer periods than the efferent suppression pathway.P2rX2knockout mice experienced much greater perma-
nent hearing loss than their wild-type littermates at sound levels
greater than 95 dB. This showed that the temporary hearing loss
evident in the wild-type mice after loud sound exposure relected
this underlying cochlear self-preservation mechanism, rather
than reversible damage. Thus, this hearing adaptation mecha-
nism, evident as sustained but recoverable hearing loss, extends
the safe upper limit for hearing.
While theP2rX2knockout mice were developed by a drug
company in the USA for a range of studies, it’s now clear that
there are naturally occurring mutations of this gene in human
populations. These genetic differences cause increased suscep-
tibility to hearing loss. In 2012 we reported that members of
families with the P2rX2 mutation who moved from a quiet
rural environment to noisy cities experienced more rapid
progressive hearing loss than their relatives who had remained
in a rural setting (tinyurl.com/ovqhvdb).
This serves to highlight the intimate balance between the
lifelong management of noise exposure and age-related stress on
the hearing organ. While temporary loss of hearing after expo-
sure to sustained loud sound may relect a natural adaptation
to protect our hearing, it’s also a reminder that the cochlea is
using all its intrinsic protective processes to save the sensory
hair cells and nerve ibres from damage.
Gary Housley holds the Chair in Physiology at UNSW Australia and is Director of the
Translational Neuroscience Facility in the School of Medical Sciences.38 | APRIL 2016
A section through the mouse cochlea showing the sensory hair cells
and their neural innervation (bright red fibres). Credit: Jeremy PinyonSign up at austscience.com
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