Tinnitus key cellular mechanisms identified

About 10% of the population is affected by hearing loss and tinnitus, a perception of sounds, such as ringing or buzzing in the ear in the absence of corresponding external sound, which typically develops after acoustic over-exposure to loud noises. Scientists have speculated that tinnitus is caused by damaged nerve cells within the ear, but so far, there are no drugs available for the treatment or prevention of the condition. The journal Hearing Research now reveals that researchers from the University of Leicester's Department of Cell Physiology and Pharmacology have discovered a cellular mechanism, which could be responsible for the development of tinnitus after exposure to loud noises. The finding could pave the way for the development of new drugs to treat tinnitus, and researchers are currently investigating potential drugs that could prevent the condition. Research leader, Dr. Martine Hamann from Leicester University explained: "We need to know the implications of acoustic over exposure, not only in terms of hearing loss but also what's happening in the brain and central nervous system. It's believed that tinnitus results from changes in excitability in cells in the brain - cells become more reactive, in this case more reactive to an unknown sound." The researchers examined cells in the brain's dorsal cochlear nucleus area, which carries acoustic signals from the ear's nerve cells into the parts of the brain that decode and 'interpret' sounds. Exposure to loud noises affects some of the neurons in the dorsal cochlear nucleus to behave in an uncontrolled manner by starting to fire erratically, which ultimately leads to tinnitus. Dr Hamann declared: "We showed that exposure to loud sound triggers hearing loss a few days after the exposure to the sound. It also triggers this uncontrolled activity in the neurons of the dorsal cochlear nucleus. This is all happening very quickly, in a matter of days." A major breakthrough was the team's discovery of the particular cellular mechanism that leads to the neurons' over-activity. They discovered that if potassium channels that help to control the nerve cell's electrical activity malfunction, the neurons are unable to return to a balanced resting state. These cells normally fire regularly and also regularly return to a resting state, yet if the potassium channels are malfunctioning, the cells are unable to return to a resting state and therefore continuously fire in random bursts, which creates the sensation of a constant noise even though there is no noise. Dr Hamann explained: "In normal conditions the channel helps to drag down the cellular electrical activity to its resting state and this allows the cell to function with a regular pattern. After exposure to loud sound, the channel is functioning less and therefore the cell is constantly active, being unable to reach its resting state and displaying those irregular bursts." Even though numerous scientists have explored the dynamics of why tinnitus occurs, this is the first time that researchers have managed to characterize the cellular bursting activity in association with specific potassium channels. The ability to identify the potassium channels in the early stages of tinnitus paves the way for the development of new potential drug treatments to prevent the condition. At present, Dr Hamann's team is exploring potential drugs that can control the damaged cells so that their erratic firing is blocked and they can revert to a resting state. The discovery of suitable drug components would mean that patients would be protected against the onset of tinnitus after experiencing acoustic overload. However, the development of a suitable drug to prevent tinnitus will take some years, given that investigations are still in their preliminary stage. Leicester University, in collaboration with Autifony Therapeutics Ltd, will continue to conduct further pharmaceutical research via a Medical Research Council Case studentship, which is set to commence in October 2012.