According to an investigation published in Nature Neuroscience, individuals who suffer with hereditary DFNA2 hearing loss are more sensitive to low frequency vibration. Findings from the study reveal previously unknown associations between touch sensitivity and hearing loss. Specialized nerve cells in the skin are responsible for all sensations individuals feel when they touch – hot, cold, smooth, rough, pressure, pain, itch, vibrations, and more. The study was conducted by Professor Thomas Jentsch of the Leibniz-Institut fur Molekulare Pharmakologie (FMP)/Max Delbruck Center for Molecular Medicine (MDC) Berlin-Buch and Professor Gary Lewin (MDC), in collaboration with clinicians from the Netherlands, Madrid, Spain and Nijmegen.

Several of the Spanish and Dutch family members who participated in the investigation suffer from hereditary DFNA2 hearing loss. DFNA2 is a genetic mutation which disrupts the function of several hair cells in the inner ear. The team was more intrigued in participants’ sense of touch than their hearing ability as they believed this mutation may also affect the sense of touch.

The pressure of sound waves cause thousands of tiny delicate hairs in the inner ear to vibrate causing the hair cells to fire off tiny electrical signals (potassium ions). These electrical signals then travel up the cochlea nerves of the auditory pathway to the brain. The potassium ions stream through a channel in the cell membrane and again out of the hair cells. In hearing-impaired individuals this potassium channel, a protein molecule called KCNQ4, is damaged by the mutation.

Jentsch said:

“But we have found that KCNQ4 is present not only in the ear, but also in some sensory cells of the skin. This gave us the idea that the mutation might also affect the sense of touch. And this is exactly what we were able to show in our research, which we conducted in a close collaboration with the lab of Gary Lewin, a colleague from the MDC who is specialized in touch sensation.”

Sense of touch allows individuals to distinguish the difference between a rough or smooth surface by the vibrations that occur in the skin when the surface is touched. Touch sensations provide a wealth of information to our brains about the environment around us. For each different touch sensation there are sensory cells in the cells with different structures – deformation of the structures generates electric nerve signals. Although precisely why this occurs remains unknown. Sense of touch is the least understood of the five senses of Aristoteles.

The discoveries of Matthias Heidenreich and Stefan Lechner from the research groups of Thomas Jentsch and Gary Lewin clearly show there are parallels to hearing. In Jentsch’s lab, the investigators first developed a mouse model for deafness by creating a mouse line that has the same mutation in the potassium channel as an individual with DFNA2. Although the defective channel did not kill the touch receptors in the skin where the KCNQ4 potassium channel is found as they did in the ear, the touch receptors demonstrated a changed electric response to the mechanical stimuli in the mouse model.

The researchers discovered the touch receptors were significantly more sensitive to vibration stimulation in the low frequency range. For potassium ions the outlet valve usually operates here as a filter to weaken the sensitivity of the cells preferentially at low frequencies. In normal individuals, this usually tunes these mechanoreceptors to moderately high frequencies. In mice without functional KCNQ4 channels, touch receptors can no longer make out the difference between low and high frequencies.

The exact same effect was observed in the deaf participants with mutations in the potassium channel, when analyzed by Lechner and Matthias Heidenreich. In addition they could distinguish very slow vibrations that their healthy siblings were unable to mark. As a result of the mutations in the KCNQ4 channel gene, the fine tuning of the mechanoreceptors for normal touch sensation was changed.

Jentsch and Lewin explained:

“The sensation of touch varies greatly from person to person – some people are much more sensitive to touch than others. DFNA2 patients are extremely sensitive to vibrations. The skin has several different types of mechanoreceptors, which respond to different qualities of stimuli, especially to different frequency ranges. The interaction of different receptor classes is important for the touch sensation. Although the receptors we studied became more sensitive due to the loss of the potassium channel, this may be outweighed by the disadvantage of the wrong “tuning to other frequencies”. With KCNQ4 we have for the first time identified a human gene that changes the traits of the touch sensation.”

The team led by Gary Lewin belongs to the MDC in Berlin and is specialized in peripheral sensory perception. The investigation team led by Thomas Jentsch belongs both to the FMP and the MDC and researches ion transport and its role in disease.

Written by Grace Rattue