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Pump Up The Volume By Vivienne Baillie Gerritsen

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 of Corti.

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 take place.

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

P58743:Human prestin References

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 1961

Protein Spotlight (ISSN 1424-4721) is published by the SWISS-PROT group at the Swiss Institute of Bioinformatics (SIB). Authorization to photocopy or reproduce this article for internal or personal use is granted by the SIB provided its content is not modified. Please enquire at spotlight@isb-sib.ch for commercial usage.





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