New research from the Stanford University School of Medicine (Stanford, California) directly challenges a roughly 25-year-old theory about how the inner ear translates vibrations in the air into sounds heard by the brain.

Anthony Ricci, PhD, associate professor of otolaryngology, and colleagues at the University of Wisconsin (Madison) and the Pellegrin Hospital (Bordeaux, France) found that the ion channels responsible for hearing aren't located where scientists previously thought. The discovery turns old theories upside down, and it could have major implications for the prevention and treatment of hearing loss, according to the researchers.

"The basic idea of how you convert a sound wave into an electrical signal was thought to be on the sensory cells, hair cells, and it seems kind of trivial, but there is a debate over where these mechanical channels are located," Ricci told Medical Device Daily.

Deep inside the ear, specialized cells, called hair cells, sense vibrations in the air. The cells contain tiny clumps of hair-like projections, known as stereocilia, arranged in rows by height. Sound vibrations cause the stereocilia to bend slightly, and scientists think the movement opens small pores, called ion channels.

As positively charged ions rush into the hair cell, mechanical vibrations are converted into an electrochemical signal that the brain interprets as sound.

But after years of searching, scientists still haven't identified the ion channels responsible for this process. To pinpoint the channels' location, Ricci and colleagues squirted rat stereocilia with a tiny water jet. As pressure from the water bent the stereocilia, calcium flooded into the hair cells. The researchers used ultrafast, high-resolution imaging to record exactly where calcium first entered the cells. Each point of entry marked an ion channel.

The results were surprising: Instead of being on the tallest rows of stereocilia, like scientists previously thought, Ricci's team found ion channels only on the middle and shortest rows. The findings will appear in the May issue of Nature Neuroscience.

"Location is important, because our entire theory of how sound activates these channels depends on it," Ricci said. "Now we have to re-evaluate the model that we've been showing in textbooks for the last 30 years."

Ion channels on hair cells not only convert mechanical vibrations into signals for the brain, but they also help protect the ear against sounds that are too loud. Through a process called adaptation, the ear adjusts the sensitivity of its ion channels to match the noise level in the environment.

To further explain this phenomenon, Ricci used the example of watching TV in bed. Even with the sound turned down low, he said, you can still hear it will while falling asleep. But then when you get up in the morning and turn on the news, you have to turn up the volume. That's because at night, when everything is quiet, the ear turns up its amplifier to hear softer sounds.

But in the morning when the kids are running around, the dog barking, the ear has to reset its sensitivity so you can hear in noisier conditions without hurting your ear, Ricci said.

"The old theory was very elegant because it was very simple, and it kind of intuitively made sense, and most people just accepted it, despite the fact that it hasn't really been validated," Ricci told MDD. He said this is the first piece of data that directly challenges that old theory.

The study was funded by grants from the National Institute on Deafness and Other Communicative Disorders. Other scientists have attempted similar experiments in the past, but Ricci said they used less-sensitive imaging techniques.

"Our microscope took images at 500 frames per second," said Ricci, who led the imaging experiments. "That's much faster than it's ever been done before."

While this discovery means that a lot of previous data related to hearing will have to be re-evaluated, Ricci said that the data in general is correct. It's just the interpretation of most of that data is incorrect.

"The existing model most likely is not correct, assuming our data is correct ... so that has to change," he said.

The research finding has drawn "some interesting feedback," Ricci said. He described it as "kind of mixed," some researchers being able to make more sense out of their own work by understanding what protein to use, others being skeptical.

"I think there [are] always the doubting Thomases ... overall [the reaction has] been pretty positive ... It's making people rethink what they've been doing, which is always good, I think," Ricci said.

He said he hopes the research will stimulate similar investigations, specifically that the new discovery will spur new data over the next year or so. "There were too many people that were just accepting what's out there, and when that happens the field doesn't move forward," Ricci said.

"I had thought that the channels were in a very different place," said Peter Gillespie, PhD, professor of otolaryngology at Oregon Health and Science University (Portland), who was not involved with the study. "This changes how we look at all sorts of previous data."

Defects in the ear's adaptation process put people at risk for both age-related and noise-related hearing loss, said Robert Jackler, MD, the Edward C. and Amy H. Sewall Professor in Otorhinolaryngology at Stanford. And understanding adaptation is a fundamental step in prevention.

"Many forms of hearing loss and deafness are due to disturbances in the molecular biology of the hair cell," said Jackler, also not involved in the study. "When you understand the nuts and bolts of how the hair cell works, you can understand how it goes wrong and can set about learning how to fix it."

Ricci and colleagues also used hair cells from rats, while previous experiments had been done in bullfrogs. Because mammals have fewer, more widely spaced rows of stereocilia, the team was able to determine the precise location of the ion channels.

"They chose their experimental preparation quite wisely," Gillespie said. "The ear is really hard to get at because it's a tiny organ, it's encased in very hard bone and there are very few hair cells."

Ricci's study wasn't just a triumph in experimental protocol; it provides a concrete clinical door-opener, according to those at Stanford. Millions of Americans suffer from hearing loss and deafness, and understanding the molecular basis of normal hearing will help to understand what can go wrong.

"We need to know specifically how hearing works," Ricci said, "or we can't come up with better treatments."

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