Reduced electromotility of outer hair cells associated with connexin-related forms of deafness: an in silico study of a cochlear network mechanism.

Journal of the Association for Research in Otolaryngology : JARO
Pavel Mistrík, J Ashmore

Abstract

Mutations in the GJB2 gene encoding for the connexin 26 (Cx26) protein are the most common source of nonsyndromic forms of deafness. Cx26 is a building block of gap junctions (GJs) which establish electrical connectivity in distinct cochlear compartments by allowing intercellular ionic (and metabolic) exchange. Animal models of the Cx26 deficiency in the organ of Corti seem to suggest that the hearing loss and the degeneration of outer hair cells (OHCs) and inner hair cells is due to failed K(+) and metabolite homeostasis. However, OHCs can develop normally in some mutants, suggesting that the hair cells death is not the universal mechanism. In search for alternatives, we have developed an in silico large scale three-dimensional model of electrical current flow in the cochlea in the small signal, linearised, regime. The effect of mutations was analysed by varying the magnitude of resistive components representing the GJ network in the organ of Corti. The simulations indeed show that reduced GJ conductivity increases the attenuation of the OHC transmembrane potential at frequencies above 5 kHz from 6.1 dB/decade in the wild-type to 14.2 dB/decade. As a consequence of increased GJ electrical filtering, the OHC transmembrane poten...Continue Reading

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Citations

May 9, 2013·Nature Communications·Yan ZhuHong-Bo Zhao
Jun 21, 2019·International Journal of Molecular Sciences·László KölesTibor Zelles
Sep 6, 2018·Cold Spring Harbor Perspectives in Medicine·Fabio Mammano

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