Chloride imbalance may cause hearing loss

Two years ago, political commentator Rush Limbaugh dismissed in his blog the importance of School of Medicine surgery and neurobiology professor Joseph Santos-Sacchi’s in vitro chloride ion and hearing study. But Limbaugh recently received a cochlear implant to help with his hearing, and Sacchi says he wonders what the talk show host would say about Sacchi’s new study, which builds on his previous work but adds a new spin — it is tested on mammals.

In a study published last week in the Journal of Neuroscience, Sacchi showed that altering the balance of chloride levels in the outer hair cells — which coil around the cochlea, or the snail shell-shaped part of the inner ear — interfered with cochlear amplification in guinea pigs. Mammals are the only animals with cochlear amplification, or the ability to hear low-level sounds. Sacchi said that understanding the role chloride ions play in hearing is the first step in learning how to solve hearing problems.

“It is possible that in the future, if a particular hearing loss is due to a chloride imbalance, it might be possible to reverse that somehow, for example by playing with drugs that would alter the homeostasis in the outer hair cell,” he said.

The binding of the chloride ion to a protein in the membrane of the outer hair cell drives cochlear amplification. Sacchi created a gradient and measured the varying levels of this amplification by manipulating chloride levels across the membrane.

Lei Song, a postdoctoral associate in surgery and otolaryngology and a co-author of the study, said the new research will not have an immediate impact in improving hearing aids, and that more research, including finding out what controls chloride levels, needs to be conducted before it can be applied to new technology or medicine.

“The next line of study is to find out what, if any, mechanism regulates intracellular chloride, because if you have a chloride channel being manipulated, you can also manipulate the output of cochlear amplification,” Song said.

To measure the guinea pigs’ hearing levels as a function of changes in chloride level, Sacchi manipulated chloride levels in the pigs by either directly altering chloride levels or administering a solution of chloride ions with tributyl tin (TBT), which occurs naturally in plants, or salicylate, which is a component in aspirin. Sacchi said the alterations of chloride levels and cochlear amplification were fully reversible.

Sacchi said he thinks TBT, an environmental toxin found in boat paint, may accumulate in the inner ear of marine mammals, potentially affecting their hearing.

“If whales or dolphins are exposed to altering chloride movements, it could be detrimental to their hearing and echolocation and cause beaching,” Sacchi said.

Sacchi said he became curious of the effects of TBT on marine mammal hearing after switching from a TBT-based paint on his own boat to a copper-based paint. TBT prevents the buildup of barnacles on the hull of the ship, thus decreasing the drag in the water, and making boats rides smoother. But because TBT has also been shown to interfere with the reproduction and hormonal levels of lower life forms in the sea, the United Nation’s International Maritime Organization has agreed to a worldwide ban of TBT by 2008.

“TBT worked very well, which is why it is still used on some big boats,” Sacchi said. “By keeping algae off these boats it saved a lot of money and lot of energy. Being on a boat, I wondered about TBT, and I knew it was a toxin; that is why we made this connection.”

Sacchi said environmentalists should attempt to measure TBT levels in dolphins and whales in understanding the causes of beaching. But Mendy Garron, a northeast region stranding coordinator at the National Oceanic and Atmospheric Administration Fisheries, said in an e-mail that a more cross-sectional study involving various possible causes, not just TBT, would be more useful.

“It can be very difficult to identify a single cause for many marine mammal strandings,” Garron said. “However, a comparative study could identify possible anthropogenic factors affecting marine mammal populations.”

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