Protein that converts sound waves into electrical waves in the cochlea discovered

For scientists who study the genetics of hearing and deafness, finding the exact genetic machinery in the inner ear that responds to sound waves and converts them into electrical impulses, the language of the brain, has been something of a holy grail.

The physical basis for hearing and mechanotransduction involves receptor cells deep in the ear that collect vibrations and convert them into electrical signals that run along nerve fibers to areas in the brain where they are interpreted as sound.

What happens in hearing is that mechanical vibration waves traveling from a sound source hit the outer ear, propagate down the ear canal into the middle ear and strike the eardrum. The vibrating eardrum moves a set of delicate bones that communicate the vibrations to a fluid-filled spiral in the inner ear known as the cochlea. .

Inside the cochlea are specialized "hair" cells that have symmetric arrays of extensions known as stereocilia protruding out from their surface. The movement of the fluid inside the cochlea causes the stereocilia to move, and this movement causes ion channels to open. The opening of these channels is a signal monitored by sensory neurons surrounding the hair cells, and when those neurons sense some threshold level of stimulation, they fire, communicating electrical signals to the auditory cortex of the brain.

Scientists at The Scripps Research Institute (TSRI) in La Jolla, CA, have identified a critical component of this ear-to-brain conversion -- a protein called TMHS. This protein is a component of the so-called mechanotransduction channels in the ear, which convert the signals from mechanical sound waves into electrical impulses transmitted to the nervous system. Not only have the scientists finally found a key protein in this process, but the work also suggests a promising new approach toward gene therapy. In the laboratory, the scientists were able to place functional TMHS into the sensory cells for sound perception of newborn deaf mice, restoring their function. In some forms of human deafness, there may be a way to stick these genes back in and fix the cells after birth," TMHS appears to be the direct link between the spring-like mechanism in the inner ear that responds to sound and the machinery that shoots electrical signals to the brain. When the protein is missing in mice, these signals are not sent to their brains and they cannot perceive sound.

Specific genetic forms of this protein have previously been found in people with common inherited forms of deafness, and this discovery would seem to be the first explanation for how these genetic variations account for hearing loss.

TMHS turns out to play a role in a molecular complex called the tip link, which several years ago was discovered to cap the stereocilia protruding out of hair cells. These tip links connect the tops of neighboring stereocilia, bundling them together, and when they are missing the hair cells become splayed apart.

But the tip links do more than just maintain the structure of these bundles. They also house some of the machinery crucial for hearing -- the proteins that physically receive the force of a sound wave and transduce it into electrical impulses by regulating the activity of ion channels. The molecules that form the tip links were identified in the same laboratory previously, but the ion channels and the molecules that connect the tip link to the ion channels remained elusive. For years, scientists have eagerly sought the exact identity of the proteins responsible for this process.

In this study scientists showed that TMHS is one of the lynchpins of this process, where it is a subunit of the ion channel that directly binds to the tip link. When the TMHS protein is missing, otherwise completely normal hair cells lose their ability to send electrical signals.

Journal Reference:

1. Wei Xiong, Nicolas Grillet, Heather M. Elledge, Thomas F.J. Wagner, Bo Zhao, Kenneth R. Johnson, Piotr Kazmierczak, Ulrich Müller. TMHS Is an Integral Component of the Mechanotransduction Machinery of Cochlear Hair Cells. Cell, 2012; 151 (6): 1283 DOI:10.1016/j.cell.2012.10.041
2. Scripps Research Institute. "Scientists identify molecules in the ear that convert sound into brain signals." ScienceDaily, 6 Dec. 2012. Web. 20 Feb. 2013.

Two-photon microscopy offers look inside intact cochlea

For the first time, researchers have snapped pictures of mouse inner ear cells using an approach that doesn’t damage tissue or require elaborate dyes. The approach could offer a way to investigate hearing loss and may help guide the placement of cochlear devices or other implants.

The small delicate cochlea and associated parts are encased in the densest bone in the body.  With standard anatomical imaging techniques such as MRI, the inner ear just looks like a small grey blob. “We can’t biopsy it, we can’t image it, so it’s very difficult to figure out why people are deaf,” said ear surgeon and neuroscientist Konstantina Stankovic of the Massachusetts Eye and Ear Infirmary in Boston.  

Stankovic and her colleagues took a peek at inner ear cells using an existing technique called two-photon microscopy. Stankovic and her colleagues took a peek at inner ear cells using an existing technique called two-photon microscopy. This approach shoots photons at the target tissue, exciting particular molecules that then emit light. The researchers worked with mice exposed to 160 decibels of sound for two hours. Then they removed the rodents’ inner ears, which includes the spiraled, snail-shaped cochlea and other organs. Instead of cutting into the cochlea, the researchers peered through the “round window” — a middle ear opening covered by a thin membrane that leads to the cochlea.

The approach yielded clear images of rows of the inner ear’s hair cells, tiny hairlike structures that detect sound vibrations, enabling hearing. Unlike in control mice, ears of noise-exposed mice had visible damage: Whole sections of ear cells were wiped out, Stankovic reported February 17 at the annual meeting of the American Association for the Advancement of Science.

She hopes the approach will not only shed light on the various kinds of damage that lead to hearing loss, but that it also will help guide the insertion of implants.  In the future, the imaging approach might help guide the placement of an experimental device that extracts energy from the inner ear, acting as a tiny battery. The new device, developed by Stankovic and colleagues, doesn’t generate enough power to run a cochlear implant. It could, however, act as a sensor, monitoring for infections or sensing drug levels.

Such devices might prove very useful for monitoring all sorts of physiological responses, says biomedical engineer Philippe Renaud of Swiss Federal Institute of Technology in Lausanne. They could prove especially useful, he says, in patients for whom devices need to be small, delicate and efficient, such as those undergoing deep brain stimulation.

Citations:

K. M. Stankovic. Treating deafness with better vision: cellular level optical imaging of the inner ear. Annual meeting of the American Association for the Advancement of Science, Boston. Presented February 17, 2013

Imaging technique offers look inside hearing loss
By Rachel Ehrenberg in Science news

http://www.sciencenews.org/view/generic/id/348394/description/Imaging_technique_offers_look_inside_hearing_loss