protein in inner ear translates sound into nerve impulses used by brain

[Guest guest]

(of interest about inherited deafness)

Researchers have identified a protein in the inner ear that translates

sound into the nerve impulses used by the brain

13-Oct-2004 News-Medical.Net

Researchers at Harvard Medical School and their colleagues report in the

October 13 Nature advanced on-line edition that they have identified a

protein deep in the inner ear that they believe translates sound into

the nerve impulses used by the brain.

" People have been looking for this protein for a decade, " says

Corey, HMS professor of neurobiology and an investigator of the

Medical Institute. Other protein candidates have been nominated,

but this is " the strongest evidence yet that this protein is the

hair-cell transduction channel, " says Corey, lead author of the paper.

The discovery could help scientists investigate normal hearing and

inherited forms of deafness, which typically involve other protein

pieces of the same acoustic apparatus, says Corey, also co-director of

the HMS Center for Hereditary Deafness.

" This is the most important molecule in the ear, " said Gillespie,

a neurobiologist at Oregon Health & Science University who recently has

helped identify important parts connecting to either side of the

channel. " This channel is the jewel everyone would like to find.

Identifying it is getting at the real kernel of how the inner ear

works. "

The protein, TRPA1 (pronounced TRIP-AY-ONE), is located at the tips of

specialized cilia on hair cells of the inner ear. Scientists believe the

protein forms pores that open and close in sync with sound waves,

allowing ions to flow into the cells and to transform the vibrations

into electric signals. The same protein channel also may help people

distinguish between tones of different frequencies.

Sound travels through the auditory system like a message relayed through

the jungle from drum to drum. Snippets of conversation or the roar of a

leaf blower are collected by the fleshy outer part of the ear and

funneled inside where a delicate percussion section vibrates, taps and

shivers.

The key elements in converting sound into nerve impulses are the bundles

of cilia that protrude from the tops of hair cells and give them their

name. Inside the cochlea, the stiff cilia bend at their bases when the

pulsing sound waves push against them thousands of times a second. Small

protein strings called tip links connect the tip of each cilium with its

taller neighbor. (Six months ago, other researchers discovered the

molecular identity of the tip links.) With each vibration, the bending

cilia pull on the links connecting them, yanking open the channels to

allow ions to flood into the cilia. The resulting voltage change

activates the conversion of sound to a nerve signal. Then, the cilia

bend back and ion channels snap shut.

" Hair cells convert a mechanical stimulus into an electrical signal with

molecular, strings, springs and levers, " Corey says. " It's cell biology,

but it's wonderfully mechanical as well. "

In their paper, Corey and his colleagues present evidence that the

mysterious ion channel is actually TRPA1. The TRP proteins are a trendy

new family of ion channels involved in sensory perception. Different TRP

proteins help insects see and hear, mammals taste and sense heat and

pheromones. A small clan known as TRPN help fruit flies sense touch and

fish hear.

At the beginning of their study, Corey and his colleagues systematically

evaluated all of the several dozen mouse TRP channels with RNA probes to

locate the ones expressed by hair cells of the mouse cochlea. TRPA1

looked most promising. Using antibodies to TRPA1, the team found that

the channels were located at the tips of hair cell cilia.

As attractive as the protein appeared, it had to pass several other

rigorous tests made possible by scientific advances in the last several

years. In zebrafish, the researchers blocked expression of the TRPA1

protein and found their hair cells did not generate electrical signals

in response to vibration. In a related test, these hair cells showed

none of the telltale glow when exposed to a fluorescent dye that usually

pours in through working transduction ion channels.

In the third set of experiments, collaborators at the University of

Virginia School of Medicine genetically blocked the TRPA1 channel in

hair cells of embryonic mice, using siRNAs carried in with adenoviruses,

and measured the response. They recorded barely any electrical activity

in the hair cells with blocked TRPA1. Likewise, the hair cells did not

take up the fluorescent dye. Although the discovery needs confirmation

by other methods, TRPA1 is the best candidate for the hair-cell

transduction channel.

What are the implications for hearing and deafness? " Other protein

components of the transduction apparatus cause inherited deafness and

blindness when mutated, " Corey says. " Although there is no evidence for

it at the moment, the same may be true for TRPA1. Having the

transduction channel will accelerate a search for the remaining protein

pieces, and these in turn may be causes of inherited deafness. "

http://www.hms.harvard.edu/