Scientists Find Molecular Key to Hearing
By Amanda Gardner, HealthDay Reporter
WEDNESDAY, Oct. 13 (HealthDayNews) -- Researchers believe they have discovered the final link in the physiological process that enables us to hear.
That last connection is a molecule in the inner ear that converts sound waves into nerve impulses used by the brain, a process known as transduction.
The discovery, which is reported in the Oct. 13 online issue of Nature, is one of the last pieces to fall into place in understanding how hearing works.
"This is very significant because it adds to our knowledge of almost subcellular workings of the inner ear," said Dr. Sujana Chandrasekhar, a clinical associate professor of otolaryngology at Mount Sinai School of Medicine and New York Eye and Ear Infirmary in New York City. "In the space of a very short period of time, we have gone from just knowing what cells look like to seeing different components in the cell. This gets to another level." Chandrasekhar was not involved with the study.
Scientists are now checking blood samples from patients where deafness seems to run in the family to see if defects in the molecule, called TRPA1, contribute to hearing loss. Even if it doesn't, "knowing the protein identity will help us find other protein constituents which may be causes of inherited deafness," said study author David P. Corey, a professor of neurobiology at Harvard Medical School and an investigator with the Howard Hughes Medical Institute. That may lead to new ways to combat deafness.
While the mechanisms behind other senses are already clearly understood, that of hearing was more elusive. In fact, researchers had been searching for this molecule for about 20 years, if not longer.
These authors took a fairly systematic approach to the problem, first identifying candidate molecules by their physiologic characteristics and finally settling on what are known as TRP channels. These "ion channels" are made of one or more proteins that span the cell membrane and that come together to make a pore through the membrane for ions to pass through.
"Many of the TRP channels are involved in sensory transduction in other animals -- for example, vision and touch in flies and hearing in flies," Corey explained.
Ultimately, it was the genome project that paved the way for the discovery. "We were able to go into databases and find TRP channels in mice, and then we made little probes that would tell us which of the various channels are made by hair cells [which populate the ear], and really only one seemed to be a candidate," Corey said.
Corey and his colleagues next interfered with the production of TRPA1 in zebrafish embryos and hair cells from mice. In cells that had lower levels of the protein, there appeared to be no channel for a dye to pass through.
Microelectrodes placed on mouse hair cells also registered less current flowing through when TRPA1 levels were reduced.
The TRPA1 molecules can be seen "as the end target of a whole chain of mechanical connections" enabling us to hear, Corey said.
The whole process is reminiscent of the board game Mouse Trap.
Sound first enters the external ear, traveling through the ear canal until it reaches the ear drum, causing it to vibrate. This then causes the three bones of the middle ear (one of them attached to the ear drum), called auditory ossicles, to vibrate as well. The auditory ossicles carry the vibrations into the inner ear and cause the fluid of the inner ear to vibrate. The fluid in the inner ear then causes a ribbon of cells called hair cells to vibrate up and down. That up and down motion causes tiny hair cells called cilia to move back and forth.
The back-and-forth motion cause the newly discovered protein, which forms pores located at the tips of the cilia, to form pores or channels that open and close in response to sound waves. When the pores open, ions flow into the cells and transform the vibrations into electrical signals.
"The current coming into the cell changes the voltage inside the cell, and then it works sort of like other cells in the nervous system," Corey said.
The change in voltage makes the hair cell release chemical signals onto secondary neurons, which generate their own electrical signals; these signals carry the information to the brain.
TRPA1 molecules might be involved in amplifying sound as well.
The finding could open the way for restoring hearing without devices, Chandrasekhar said. "If we know that the absence of TRPA1 is a problem, can we then deliver TRPA1 genetically into the inner ear without opening it up and replace something that is missing or something that has been lost, and get the cells to move again?" she asked. "We have not yet figured out how to do that in a living being."
The discovery, Chandrasekhar said, is "one giant step for proteins, and one small but very meaningful step for hearing restoration."
More information
For more on hearing and deafness, visit the National Institutes on Deafness and Other Communicative Disorders (www.nidcd.nih.gov ). 
SOURCES: David P. Corey, Ph.D., professor, neurobiology, Harvard Medical School, Boston and investigator, Howard Hughes Medical Institute; Sujana Chandrasekhar, M.D., clinical associate professor, otolaryngology, Mount Sinai School of Medicine and New York Eye and Ear Infirmary, New York City; Oct. 13, 2004, Nature online
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