Tonotopy in calcium homeostasis and vulnerability of cochlear hair cells

Publication date: Available online 16 November 2018

Source: Hearing Research

Author(s): Robert Fettiplace, Jong-Hoon Nam

Abstract

Ototoxicity, noise overstimulation, or aging, can all produce hearing loss with similar properties, in which outer hair cells (OHCs), principally those at the high-frequency base of the cochlea, are preferentially affected. We suggest that the differential vulnerability may partly arise from differences in Ca²⁺ balance among cochlear locations. Homeostasis is determined by three factors: Ca²⁺ influx mainly via mechanotransducer (MET) channels; buffering by calcium-binding proteins and organelles like mitochondria; and extrusion by the plasma membrane CaATPase pump. We review quantification of these parameters and use our experimentally-determined values to model changes in cytoplasmic and mitochondrial Ca²⁺ during Ca²⁺ influx through the MET channels. We suggest that, in OHCs, there are two distinct micro-compartments for Ca²⁺ handling, one in the hair bundle and the other in the cell soma. One conclusion of the modeling is that there is a tonotopic gradient in the ability of OHCs to handle the Ca²⁺ load, which correlates with their vulnerability to environmental challenges. High-frequency basal OHCs are the most susceptible because they have much larger MET currents and have smaller dimensions than low-frequency apical OHCs.

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