Onset kinetics of noise-induced purinergic adaptation of the ‘cochlear amplifier’
- 81 Downloads
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.
KeywordsDistortion product otoacoustic emission P2X2 receptor Auditory brainstem response Noise-induced hearing loss Temporary threshold shift Mouse
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.
Compliance with ethical standards
Conflicts of interest
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.
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.
- 2.Sadhra S, Jackson CA, Ryder T, Brown MJ (2002) Noise exposure and hearing loss among student employees working in university entertainment venues. Ann Occup Hyg 46(5):455–463Google Scholar
- 7.Miller JD, Watson CS, Covell WP (1963) Deafening effects of noise on the cat. Acta Otolaryngol 1276:1–91Google Scholar
- 9.Housley GD, Morton-Jones R, Vlajkovic SM, Telang RS, Paramananthasivam V, Tadros SF, Wong AC, Froud KE, Cederholm JM, Sivakumaran Y, Snguanwongchai P, Khakh BS, Cockayne DA, Thorne PR, Ryan AF (2013) ATP-gated ion channels mediate adaptation to elevated sound levels. Proc Natl Acad Sci U S A 110(18):7494–7499. https://doi.org/10.1073/pnas.1222295110 CrossRefGoogle Scholar
- 10.Morton-Jones RT, Vlajkovic SM, Thorne PR, Cockayne DA, Ryan AF, Housley GD (2015) Properties of ATP-gated ion channels assembled from P2X2 subunits in mouse cochlear Reissner’s membrane epithelial cells. Purinergic Signal 11(4):551–560. https://doi.org/10.1007/s11302-015-9473-4
- 12.Wang JC, Raybould NP, Luo L, Ryan AF, Cannell MB, Thorne PR, Housley GD (2003) Noise induces up-regulation of P2X2 receptor subunit of ATP-gated ion channels in the rat cochlea. Neuroreport 14(6):817–823. https://doi.org/10.1097/01.wnr.0000067784.69995.47
- 13.Housley GD, Luo L, Ryan AF (1998) Localization of mRNA encoding the P2X2 receptor subunit of the adenosine 5′-triphosphate-gated ion channel in the adult and developing rat inner ear by in situ hybridization. J Comp Neurol 393(4):403–414Google Scholar
- 14.Greenwood D, Jagger DJ, Huang LC, Hoya N, Thorne PR, Wildman SS, King BF, Pak K, Ryan AF, Housley GD (2007) P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea. Development 134(7):1407–1417. https://doi.org/10.1242/dev.002279 CrossRefGoogle Scholar
- 15.Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fujikawa T, Wong AC, Loh TL, Du L, Grati M, Vlajkovic SM, Blanton S, Ryan AF, Chen ZY, Thorne PR, Kachar B, Tekin M, Zhao HB, Housley GD, King MC, Liu XZ (2013) Mutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noise. Proc Natl Acad Sci U S A 110(6):2228–2233. https://doi.org/10.1073/pnas.1222285110
- 16.Moteki H, Azaiez H, Booth KT, Hattori M, Sato A, Sato Y, Motobayashi M, Sloan CM, Kolbe DL, Shearer AE, Smith RJ, Usami S (2015) Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation. Ann Otol Rhinol Laryngol 124(Suppl 1):177S–183S. https://doi.org/10.1177/0003489415575045 CrossRefGoogle Scholar
- 22.Shaffer LA, Withnell RH, Dhar S, Lilly DJ, Goodman SS, Harmon KM (2003) Sources and mechanisms of DPOAE generation: implications for the prediction of auditory sensitivity. Ear Hear 24(5):367–379. https://doi.org/10.1097/01.AUD.0000090439.16438.9F CrossRefGoogle Scholar
- 31.Vlajkovic SM, Thorne PR, Housley GD, Munoz DJ, Kendrick IS (1998) Ecto-nucleotidases terminate purinergic signalling in the cochlear endolymphatic compartment. Neuroreport 9(7):1559–1565Google Scholar
- 42.Syka J, Melichar I, Ulehlova L (1981) Longitudinal distribution of cochlear potentials and the K+ concentration in the endolymph after acoustic trauma. Hear Res 4(3–4):287–298Google Scholar
- 43.Melichar I, Syka J, Ulehlova L (1980) Recovery of the endocochlear potential and the K+ concentrations in the cochlear fluids after acoustic trauma. Hear Res 2(1):55–63Google Scholar
- 49.Anselmi F, Hernandez VH, Crispino G, Seydel A, Ortolano S, Roper SD, Kessaris N, Richardson W, Rickheit G, Filippov MA, Monyer H, Mammano F (2008) ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear. Proc Natl Acad Sci U S A 105(48):18770–18775. https://doi.org/10.1073/pnas.0800793105 CrossRefGoogle Scholar