Skip Navigation LinksHome > August 2013 - Volume 66 - Issue 8 > Editorial: Tinnitus Induction: A Departure from Tradition
Hearing Journal:
doi: 10.1097/01.HJ.0000433569.96246.9e
Editorial

Editorial: Tinnitus Induction: A Departure from Tradition

Kaltenbach, James A. PhD

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Dr. Kaltenbach is professor and director of otology research in the Department of Neurosciences at the Cleveland Clinic, as well as professor of molecular medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

It is widely believed that tinnitus results from a hyperactive state in neurons of the central auditory system. Hyperactivity is observed at multiple levels of the auditory system in animals and humans with tinnitus but has been most thoroughly investigated in the dorsal cochlear nucleus (DCN), which lies in the lower brain stem.

Figure. James A. Kal...
Figure. James A. Kal...
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Following intense noise exposure, hyperactivity is found throughout much of the DCN, but it reaches its most extreme level in the region of the nucleus coding for high frequencies. This is thought to be one of the main reasons tinnitus is most often high in pitch.

A study by Li and colleagues published online before print in Proceedings of the National Academy of Sciences of the United States of America sheds new light on the cellular defect underlying the hyperactive state of DCN neurons. The cell type in question is called the fusiform cell, a major source of hyperactivity that develops after loud sound exposure.

Hyperactive fusiform cells displayed an abnormality of a certain type of potassium channel present in the cell membrane, called the KCNQ channel, the team of investigators reported. This particular channel type is of interest because it controls the excitability of neurons. Blocking this channel or reducing its numbers causes fusiform cells to fire at higher rates.

Several aspects of this new research study are noteworthy. First, potassium channel abnormality was strongly correlated with tinnitus. This finding was demonstrated with a behavioral test called the gap detection test. Roughly half of the animals exposed to intense sound developed tinnitus; the other half did not. KCNQ channels were reduced in the animals with tinnitus but not in the animals without tinnitus.

Equally striking, the abnormally low channel expression was found in the high frequency part of the DCN, but not in the low frequency part. This observation correlates well with both the high frequency of tinnitus and the region of the DCN showing hyperactivity.

Perhaps most important, when given a drug called retigabine, which activates the KCNQ channels, many of the loud sound-exposed animals failed to develop tinnitus after noise exposure.

These findings are significant because, until now, most thinking about the underlying cellular basis of tinnitus focused on synapses—the connections between neurons that allow them to communicate with each other.

Synapses come in two general categories: those that excite other neurons and those that inhibit them. For many years, evidence has converged on the view that tinnitus-related hyperactivity results from a shift in the balance of these two types of synapses—i.e., an increase in the strength of excitatory synapses or a decrease in the strength of inhibitory synapses.

The study by Li and colleagues is the first to show evidence linking tinnitus to changes in ion channels. This work breaks fresh new ground in our understanding of tinnitus mechanisms, which is essential if research is to lead to improvements in tinnitus therapy.

© 2013 by Lippincott Williams & Wilkins, Inc.

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