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Onset kinetics of noise-induced purinergic adaptation of the ‘cochlear amplifier’

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Abstract

A major component of slowly reversible hearing loss which develops with sustained exposure to noise has been attributed to release of ATP in the cochlea activating P2X2 receptor (P2X2R) type ATP-gated ion channels. This purinergic humoral adaptation is thought to enable the highly sensitive hearing organ to maintain function with loud sound, protecting the ear from acoustic overstimulation. In the study that established this hearing adaptation mechanism as reported by Housley et al. (Proc Natl Acad Sci U S A 110:7494–7499, 2013), the activation kinetics were determined in mice from auditory brainstem response (ABR) threshold shifts with sustained noise presentation at time points beyond 10 min. The present study was designed to achieve finer resolution of the onset kinetics of purinergic hearing adaptation, and included the use of cubic (2f1–f2) distortion product otoacoustic emissions (DPOAEs) to probe whether the active mechanical outer hair cell ‘cochlear amplifier’ contributed to this process. We show that the ABR and DPOAE threshold shifts were largely complete within the first 7.5 min of moderate broadband noise (85 dB SPL) in wildtype C57Bl/6J mice. The ABR and DPOAE adaptation rates were both best fitted by a single exponential function with ~ 3 min time constants. ABR and DPOAE threshold shifts with this noise were minimal in mice null for the P2rx2 gene encoding the P2X2R. The findings demonstrate a considerably faster purinergic hearing adaptation to noise than previously appreciated. Moreover, they strongly implicate the outer hair cell as the site of action, as the DPOAEs stem from active cochlear electromotility.

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Funding

This work was supported by the National Health and Medical Research Council (NH&MRC), Australia grants APP630618 and APP1089838, and the Research Service of the US Veterans Administration grants BX001205 and RX000977.

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Authors and Affiliations

  1. Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia

    Jennie M. E. Cederholm & Gary D. Housley

  2. Departments of Surgery and Neurosciences, University of California San Diego, La Jolla, CA, USA

    Allen F. Ryan

  3. Veterans Administration Medical Center, La Jolla, CA, USA

    Allen F. Ryan

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  1. Jennie M. E. Cederholm
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  3. Gary D. Housley
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Correspondence to Gary D. Housley.

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Jennie M. E. Cederholm declares that he/she has no conflict of interest.

Allen F. Ryan declares that he/she has no conflict of interest.

Gary D. Housley declares that he/she has no conflict of interest.

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All experimental procedures for the mice were reviewed and approved by the UNSW Sydney Animal Care and Ethics Committee.

Declaration of interest statement

The authors declare that the findings of this study form part of a patent filing by New South Innovations Pty Ltd., the commercialization arm of UNSW Sydney (the assignee), for a method for predicting vulnerability to hearing loss.

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Cederholm, J.M.E., Ryan, A.F. & Housley, G.D. Onset kinetics of noise-induced purinergic adaptation of the ‘cochlear amplifier’. Purinergic Signalling 15, 343–355 (2019). https://doi.org/10.1007/s11302-019-09648-3

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