Have you ever been to a loud concert and upon stepping out into a quieter lounge area, experienced a muffled sensation or a persistent ringing in your ears? Something has definitely happened within your ear, but have you ever wondered what exactly is being affected? To provide some context, the sensory epithelium involved in auditory processes is known as the organ of Corti. This sensory epithelium consists of hair cells, the basilar membrane, and the tectorial membrane that are located in the inner ear of the cochlea. Current research proposes that hearing sensitivity is regulated by the tectorial membrane.
Within the research article, Critical role of hepsin/TMPRSS1 in hearing and tectorial membrane morphogenesis: insights from transgenic mouse models, Dr. Yu and his colleagues did research on knock out (KO) hepsin mice that had profound hearing loss. While hepsin is a transmembrane serine protease that is also highly expressed in the liver, the mice were found to have deficits in hearing per auditory brainstem recording tests. Dr. Yu wondered if the hearing deficit was secondary to the outer hair cells in the ear but after doing a test called distortion product otoacoustic emissions (DPOE), they found that the fitness of the outer hair cells were not the cause of the hearing loss. They measured the DPOE’s in the low frequency range of the KO hepsin mice which were within normal limits but there was a problem in the high frequency range which the researchers detected arose from the tectorial membrane (TM). Using electron microscopy it was found that these protease dead mutants of hepsin mice did not have a normal area of TM to be compact and attached to the spiral limbus but rather it was more detached and had more sparse and spaced. This led the researchers to believe that the hepsin protease function is essential in hearing and hearing deficits were due to the TM. Fifty percent of the tectorial membrane consists of non-collagen properties and the most abundant are the tectorin A and B proteins. The researchers hypothesis is that hepsin can mediate the cleavage of the tectorins which contain the Zona Pellucida (ZP). In order for the tectorins to polymerize with the TM they need to undergo the proteolytic cleavage secondary to hepsin in order to expose their ZP which triggers the polymerization. If this cannot happen it leads to the gaps in the TM which contribute to the hearing loss seen in protease dead hepsin mice.
With consideration to Dr. Yu’ et al. findings, it is clear that the TM has a critical role in auditory function. In a paper called Control of hearing sensitivity by tectorial membrane calcium, Dr. Strimbu et al. explores another aspect of the TM that emphasizes the changes in calcium concentration within the tectorial membrane that contributes to hearing sensitivity. With the experiments they conducted they mentioned that “...relatively mild loud sound exposures, similar to that experienced by many people at rock concerts, there was a significant decrease in the Ca2+ of the tectorial membrane” (Strimbu, 2019). This paper underlies that when it comes to hearing, the TM that is an extracellular connective tissue covering mechanically-sensitive hair bundles of hair cells, directly influences MET channels which are located on the tips of hair cells. Therefore, exposure to loud sounds depletes calcium in the tectorial membrane and that can reduce the amplitude of microphonic potentials which was a testing tool used to look at MET channel performance. As mentioned from Dr. Yu’s paper, the role of tectorin’s were important in maintaining the structure of the TM and interestingly, tectorin A also known as alpha tectorin, is one of the binding sites for calcium. The TM is what stabilizes calcium levels and with loud noise exposure, calcium in the TM gets depleted and it is further mentioned that it could cause the tip links that have the MET channel to break based on experiments they conducted. Overall, Dr. Strimbu and his colleague’s findings explain why we might have ringing in our ear or a muffled sensation after loud noise exposure based on the mechanism where there is calcium depletion from the tectorial membrane that interacts with hair cells to stop functioning properly and when calcium ion concentration is back to its baseline, the hair cells function normally again.
In all, we can see that hearing is influenced by the tectorial membrane, whether its structural changes that induce hearing loss as seen in Dr. Yu’s findings or changes in mechanical properties of the TM per Dr. Strimbu’s findings. Interestingly, we can see that in Dr. Yu’s paper the morphology of the TM was affected since the tectorins were unable to undergo proteolytic cleavage and polymerize with the TM. Then it is learned from Dr. Strimbu that tectorin A also plays an important role in hearing since it acts as a calcium binding site in the TM. Thus, without a functioning tectorin protein we can indicate that there is hearing loss secondary to hepsin knock out but if tectorin protein is intact, it plays a role in hearing sensitivity as indicated by Dr. Strimbu and his colleagues work.
References
Strimbu, C. E., Prasad, S., Hakizimana, P., & Fridberger, A. (2019). Control of hearing sensitivity by tectorial membrane calcium. Proceedings of the National Academy of Sciences of the United States of America, 116(12), 5756–5764. https://doi.org/10.1073/pnas.1805223116
Yang, T. H., Hsu, Y. C., Yeh, P., Hung, C. J., Tsai, Y. F., Fang, M. C., Yen, A. C. C., Chen, L. F., Pan, J. Y., Wu, C. C., Liu, T. C., Chung, F. L., Yu, W. M., & Lin, S. W. (2024). Critical role of hepsin/TMPRSS1 in hearing and tectorial membrane morphogenesis: Insights from transgenic mouse models. Hearing research, 453, 109134. https://doi.org/10.1016/j.heares.2024.109134
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