Pump Up The Volume By Vivienne
There is not much we would hear without our cochlea. Our
what? The cochlea is a part of our inner ear and looks remarkably
like a snail's shell. This minute masterpiece of mammal physiology
- only a few millimeters large - has been inspected by many.
Today we know that the cochlea acts as a sound amplifier and
without it the noises which surround us would be mere fuzz.
How does it amplify sound? There is some controversy here
but one theory is based on the behavior of a modest-sized
protein: prestin. Besides the fact that prestin is at the
heart of sound amplification theories, it also happens to
be quite a particular protein. Indeed, prestin is the only
cellular motor to date which does not need the help of biological
energy, such as ATP, to function.
First though, some history on the biophysics of hearing.
The understanding of hearing stretches back to the 6th century.
Pythagorus reasoned that sound was a vibration in the air.
His followers showed that the membrane in our outer ear, the
eardrum, vibrated in response to sound and this was how it
was transmitted further inside the ear. Not much progress
was made until the 16th century when the existence of three
ossicles were described in the middle ear: the hammer, the
anvil and the stirrup, respectively. And in 1561, the snail-shaped
cochlea was discovered. Two hundred years later, the Italian
anatomist Alfonso Corti (1822-1876) had a closer look at the
cochlea. A cross section revealed a rather complicated structure
which nests within three 'tubes' bathed in fluid and follows
the length of the cochlea; he named this structure the organ
The organ of Corti is characterized by rows of inner hair
cells and outer hair cells which coat a membrane known as
the basilar membrane. A second membrane, the tectorial membrane,
caps the rows of outer hair cells. Thanks to two eminent scientists,
the great German scientist Herman Helmholtz (1821-1894) and
the Hungarian physicist Georg von Bekesy (1899-1972), it is
now clear that the organ of Corti is the playing field for
sound. And recently, on the molecular level, prestin was shown
to have evidently a fundamental role in the transmission of
sound to the brain.
Figure 1 Cross section of the cochlea and, towards its center,
the organ of Corti. The yellowish nerve endings form the basilar
membrane. The tectorial membrane is the pink structure above.
The stereocilia of the outer hair cells make contact with
the tectorial membrane. Source: http://www.olemiss.edu/working/clt/ASAPP/
So what did these two scientists discover? Helmholtz was
one of the first to propound that sensations of any kind were
of a physico-chemical nature. In the field of physiological
acoustics, he suggested that the basilar membrane in the organ
of Corti vibrates in response to sound entering the ear. However,
it was von Bekesy who managed to prove it. Von Bekesy worked
in the research laboratory of the Hungarian Post Office where
his task was to improve the communication. To do so, he studied
the tissues of a number of corpses' ears to unravel the mechanics
of the inner ear. Following Helmhotz' discovery, he was aware
that the basilar membrane was of great importance and managed
to make a number of measurements which proved what the German
scientist had assumed: the existence of traveling waves along
the basilar membrane. And not only did the basilar membrane
vibrate in response to sound but it also amplified the sound
so that it would be loud enough to be transmitted to the brain.
This is where prestin steps in. So far we know that sound
hits the eardrum causing it to beat. The beats are passed
on to the three ossicles, the last of which stirs the basilar
membrane. Then what? The stereocilia on the outer hair cells
- which coat the basilar membrane - push against the tectorial
membrane above. This causes the stereocilia to bend to one
side, a bit like a sea current brushing the tentacles of sea
anemone into the direction of the current. The subsequent
movement opens pores in the stereocilia and potassium ions
seep in creating an electric current. Prestin is a transmembrane
protein and found at the base of every outer hair cell and
acts as an anion transporter when it senses a change in transmembrane
potential. Nothing new you think. Here is the novelty: prestin
does not transport the anions but plays ping pong with them.
It catches anions floating around the cytoplasm and swings
them to the other side of the membrane in response to hyperpolarization.
Only instead of letting them free, in response to depolarization,
it flings them back into the cytoplasm. This ping-pong movement
is extremely rapid and creates conformational changes in the
protein, which lengthens and shortens depending on the presence
or absence of anions, respectively. As one could expect, the
net result is a lengthening and shortening of the outer hair
cells themselves in response to sound. So here is a semi-transporter
- in effect a cellular motor - which does not involve any
enzymatic process, such as the ATP/GTP hydrolysis, as all
other cellular motors known to date do.
Regarding sound amplification in the ear, it is believed
by some that the pumping movement caused by the lengthening
and shortening of prestin within the cells' membranes may
be a means of amplifying sound which otherwise would be too
weak to be transmitted to the brain. How? The pumping of the
outer hair cells, caused by the conformational changes of
prestin in response to the initial sound vibration, is fed
back to the basilar membrane. This feedback oscillation, or
amplification, can then be fed into the inner hair cells which
then transmit electric signals to nerves and hence to the
brain. In effect, without the amplification of sound which
occurs in the outer hair cells, our perception of sound would
be 100 times less effective! For this reason, it is thought
that mutations of prestin could be at the heart of congenital
loss of hearing since the cochlear amplification would not
However, besides the probable implications of prestin in
helping those hard in hearing, it is of great interest in
the field of nanotechnology. Indeed, here is a minute cellular
motor which converts electricity into a mechanical force…and
very fast. In fact, it is the fastest cellular motor protein
know to date - hence its name borrowed from the musical notation
'presto'. And what's more, it requires no extra biological
energy such as ATP. It functions purely on the conversion
of electricity flow into a mechanical force. This makes it
a particularly precious molecule. It could be used for example
to build rapid biological machines, such as pumps within artificial
membranes, which could ultimately deliver specific drugs.
One could also imagine its use as a sensor of mechanical stress
or even as a condenser in electrical nanocircuits.
Cross-references to Swiss-Prot
1. Dallos P., Fakler B. Prestin, a new type of motor protein
Nat Rev Mol Cell Biol. 3:104-111(2002). PMID: 11836512
2. Holley M., Kachar B. Hi-fi cells at the heart of the
ear The New Scientist magazine, vol. 137, issue 1866, March
27th 1993, page 27
3. Von Bekesy G. Concerning the pleasures of observing,
and the mechanics of the inner ear Nobel lecture, 11th December
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