Skip to main content
Log in

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

  • Original Article
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

Abstract

Extracellular adenosine triphosphate (ATP) has profound effects on the cochlea, including an effect on the regulation of the endocochlear potential (EP). Noise-induced release of ATP into the endolymph activates a shunt conductance mediated by P2X2 receptors in tissues lining the endolymphatic compartment, which reduces the EP and, consequentially, hearing sensitivity. This may be a mechanism of adaptation or protection from high sound levels. As inaction of such a process could contribute to hearing loss, this study examined whether the action of ATP on EP changes with age and noise exposure in the mouse. The EP and the endolymphatic compartment resistance (CoPR) were measured in mice (CBA/CaJ) aged between 3 and 15 months. The EP and CoPR declined slightly with age with an associated small, but significant, reduction in auditory brainstem response thresholds. ATP (100–1,000 μM) microinjected into the endolymphatic compartment caused a dose-dependent decline in EP correlated to a similar decrease in CoPR. This was blocked by pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate, consistent with a P2X2 receptor-mediated shunt conductance. There was no substantial difference in the ATP response with age. Noise exposure (octave-band noise 80–100 decibels sound pressure level (dBSPL), 48 h) in young animals induced an upregulation of the P2X2 receptor expression in the organ of Corti and spiral limbus, most noticeably with the 90-dB exposure. This did not occur in the aged animals except following exposure at 90 dBSPL. The EP response to ATP was muted in the noise-exposed aged animals except following the 90-dB exposure. These findings provide some evidence that the adaptive response of the cochlea to noise may be reduced in older animals, and it is speculated that this could increase their susceptibility to noise-induced injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ABR:

Auditory brainstem response

ATP:

Adenosine 5′-triphosphate

CoPR:

Cochlear partition resistance

dBSPL:

Decibels sound pressure level

EP:

Endocochlear potential

PPADS:

Pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate

PTS:

Permanent threshold shift

TTS:

Temporary threshold shift

References

  1. Housley GD, Thorne PR (2000) Purinergic signalling: an experimental perspective. J Auton Nerv Syst 81:139–145

    Article  CAS  PubMed  Google Scholar 

  2. Housley GD, Jagger DJ, Greenwood D, Raybould NP, Salih SG, Jarlebark LE, Vlajkovic SM, Kanjhan R, Nikolic P, Munoz DJ, Thorne PR (2002) Purinergic regulation of sound transduction and auditory neurotransmission. Audiol Neuro-otol 7:55–61

    Article  CAS  Google Scholar 

  3. Thorne PR, Munoz DJ, Nikolic P, Mander L, Jagger DJ, Greenwood D, Vlajkovic S, Housley GD (2002) Potential role of purinergic signalling in cochlear pathology. Audiol Neuro-otol 7:180–184

    Article  CAS  Google Scholar 

  4. Housley GD, Bringmann A, Reichenbach A (2009) Purinergic signaling in special senses. Trends Neurosci 32:128–141

    Article  CAS  PubMed  Google Scholar 

  5. Thorne PR, Munoz DJ, Housley GD (2004) Purinergic modulation of cochlear partition resistance and its effect on the endocochlear potential in the guinea pig. J Assoc Res Otolaryngol 5:58–65

    Article  PubMed  Google Scholar 

  6. Sueta T, Paki B, Everett AW, Robertson D (2003) Purinergic receptors in auditory neurotransmission. Hear Res 183:97–108

    Article  CAS  PubMed  Google Scholar 

  7. Weisz C, Glowatzki E, Fuchs P (2009) The postsynaptic function of type II cochlear afferents. Nature 461:1126–1129

    Article  CAS  PubMed  Google Scholar 

  8. Tritsch NX, Yi E, Gale JE, Glowatzki E, Bergles DE (2007) The origin of spontaneous activity in the developing auditory system. Nature 450:50–55

    Article  CAS  PubMed  Google Scholar 

  9. Munoz DJB, McFie C, Thorne PR (1999) Modulation of cochlear blood flow by extracellular purines. Hear Res 127:55–61

    Article  CAS  PubMed  Google Scholar 

  10. Bobbin RP (2001) ATP-induced movement of the stalks of isolated cochlear Deiters’ cells. NeuroReport 12:2923–2926

    Article  CAS  PubMed  Google Scholar 

  11. Chen C, Bobbin RP (1998) P2X receptors in cochlear Deiters’ cells. Br J Pharmacol 124:337–344

    Article  CAS  PubMed  Google Scholar 

  12. Skellett RA, Chen C, Fallon M, Nenov AP, Bobbin RP (1997) Pharmacological evidence that endogenous ATP modulates cochlear mechanics. Hear Res 111:42–54

    Article  CAS  PubMed  Google Scholar 

  13. 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 134:1407–1417

    Article  CAS  PubMed  Google Scholar 

  14. Huang LC, Greenwood D, Thorne PR, Housley GD (2005) Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochlea. J Comp Neurol 484:133–143

    Article  CAS  PubMed  Google Scholar 

  15. Huang LC, Ryan AF, Cockayne DA, Housley GD (2006) Developmentally regulated expression of the P2X3 receptor in the mouse cochlea. Histochem Cell Biol 125:681–692

    Article  CAS  PubMed  Google Scholar 

  16. Piazza V, Ciubotaru CD, Gale JE, Mammano F (2007) Purinergic signalling and intercellular Ca2+ wave propagation in the organ of Corti. Cell Calcium 41:77–86

    Article  CAS  PubMed  Google Scholar 

  17. King M, Housley GD, Raybould NP, Greenwood D, Salih SG (1998) Expression of ATP-gated ion channels by Reissner’s membrane epithelial cells. NeuroReport 9:2467–2474

    Article  CAS  PubMed  Google Scholar 

  18. Sage CL, Marcus DC (2002) Immunolocalization of P2Y4 and P2Y2 purinergic receptors in strial marginal cells and vestibular dark cells. J Membr Biol 185:103–115

    Article  CAS  PubMed  Google Scholar 

  19. 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 14:817–823

    Article  CAS  PubMed  Google Scholar 

  20. Housley GD, Thorne PR, Vlajkovic SM, Morton-Jones RT, Khakh BS, Cockayne DA, Ryan AF (2008) ATP-mediated humoral inhibition of sound transduction supplants neural efferent inhibition at high sound levels as the mechanism for expanding the dynamic range of hearing. In: Santi PA (ed) 31st Annual Mid Winter Research Meeting of the Association for Research in Otolaryngology, vol. 31, Phoenix, Arizona, USA, 600, pp 204–205

  21. Afework M, Burnstock G (2000) Localization of P2X receptors in the guinea pig adrenal gland. Cells Tissues Organs 167:297–302

    Article  CAS  PubMed  Google Scholar 

  22. Afework M, Burnstock G (2000) Age-related changes in the localization of P2X (nucleotide) receptors in the rat adrenal gland. Int J Dev Neurosci 18:515–520

    Article  CAS  PubMed  Google Scholar 

  23. Koga T, Takata Y, Kobayashi K, Fujii K, Nagao T, Fujishima M (1992) Age-related changes in P2-purinergic receptors on vascular smooth muscle and endothelium. Hypertension 19:286–289

    CAS  PubMed  Google Scholar 

  24. Konishi C, Naito Y, Ohara N (1999) Age-related changes in adenosine 5′-triphosphate-induced constriction of isolated, perfused mesenteric arteries of rats. Life Sci 64:1265–1273

    Article  CAS  PubMed  Google Scholar 

  25. Krishnaraj R (1992) Negative modulation of human NK cell activity by purinoceptors. 1. Effect of exogenous adenosine triphosphate. Cell Immunol 141:306–322

    Article  CAS  PubMed  Google Scholar 

  26. Krishnaraj R (1992) Negative modulation of human NK cell activity by purinoceptors. 2. Age-associated, gender-specific partial loss of sensitivity to ATP. Cell Immunol 144:11–21

    Article  CAS  PubMed  Google Scholar 

  27. Ragazzi E, Chinellato A, Pandolfo L, Froldi G, Caparrotta L, Aliev G, Prosdocimi M, Fassina G (1995) Endothelial nucleotide-mediated aorta relaxation in aged Watanabe heritable hyperlipidemic rabbits. J Cardiovasc Pharmacol 26:119–126

    Article  CAS  PubMed  Google Scholar 

  28. Thorne PR, Chung M, Muñoz DJB, Wit HP, Housley GD (2006) Regulation of the endocochlear potential by ATP. 43rd Inner Ear Biology Workshop, Montpellier, France, p 53

  29. Zheng QY, Johnson KR, Erway LC (1999) Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear Res 130:94–107

    Article  CAS  PubMed  Google Scholar 

  30. Ohlemiller KK, Gagnon PM (2007) Genetic dependence of cochlear cells and structures injured by noise. Hear Res 224:34–50

    Article  CAS  PubMed  Google Scholar 

  31. Sewell WF (1984) The effects of furosemide on the endocochlear potential and auditory-nerve fiber tuning curves in cats. Hear Res 14:305–314

    Article  CAS  PubMed  Google Scholar 

  32. Marcus DC, Wu T, Wangemann P, Kofuji P (2002) KCNJ10 (Kir4.1) potassium channel knockout abolishes endocochlear potential. Am J Physiol 282:C403–C407

    CAS  Google Scholar 

  33. Wangemann P (2002) K+ cycling and the endocochlear potential. Hear Res 165:1–9

    Article  CAS  PubMed  Google Scholar 

  34. Salt AN, Konishi T (1979) Effects of noise on cochlear potentials and endolymph potassium concentration recorded with potassium-selective electrodes. Hear Res 1:343–363

    Article  CAS  PubMed  Google Scholar 

  35. Wang J, Li Q, Dong W, Chen J (1992) Effects of various noise exposures on endocochlear potentials correlated with cochlear gross responses. Hear Res 59:31–38

    Article  CAS  PubMed  Google Scholar 

  36. Wang L (1992) Effects of furosemide on endocochlear potentials, auditory action potentials and summating potentials and the changes of inner ear pathology. Zhonghua Er Bi Yan Hou Ke Za Zhi 27(70–2):124

    Google Scholar 

  37. Benitez LD, Eldredge DH, Templer JW (1972) Temporary threshold shifts in chinchilla: electrophysiological correlates. J Acoust Soc Am 52:1115–1123

    Article  CAS  PubMed  Google Scholar 

  38. Boettcher FA, Gratton MA, Schmiedt RA (1995) Effects of noise and age on the auditory system. Occup Med 10:577–591

    CAS  PubMed  Google Scholar 

  39. Boettcher FA, Mills JH, Dubno JR, Schmiedt RA (1995) Masking of auditory brainstem responses in young and aged gerbils. Hear Res 89:1–13

    Article  CAS  PubMed  Google Scholar 

  40. Boettcher FA, Schmiedt RA (1995) Distortion-product otoacoustic emissions in Mongolian gerbils with resistance to noise-induced hearing loss. J Acoust Soc Am 98:3215–3222

    Article  CAS  PubMed  Google Scholar 

  41. Hirose K, Liberman MC (2003) Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea. J Assoc Res Otolaryngol 4:339–352

    Article  PubMed  Google Scholar 

  42. Ma YL, Gerhardt KJ, Curtis LM, Rybak LP, Whitworth C, Rarey KE (1995) Combined effects of adrenalectomy and noise exposure on compound action potentials, endocochlear potentials and endolymphatic potassium concentrations. Hear Res 91:79–86

    Article  CAS  PubMed  Google Scholar 

  43. Ide M, Morimitsu T (1990) Long term effects of intense sound on endocochlear DC potential. Auris Nasus Larynx 17:1–10

    CAS  PubMed  Google Scholar 

  44. Ide M, Morimitsu T (1990) Long-term effects of intense sound on hair cells of Corti’s organ and endocochlear DC potential. Auris Nasus Larynx 17:61–67

    CAS  PubMed  Google Scholar 

  45. Wang JA, Dong WJ, Chen JS (1990) Changes in endocochlear potential during anoxia after intense noise exposure. Hear Res 44:143–149

    Article  CAS  PubMed  Google Scholar 

  46. Ohlemiller KK (2008) Recent findings and emerging questions in cochlear noise injury. Hear Res 245:5–17

    Article  PubMed  Google Scholar 

  47. Thorne PR, Chung M, Munoz DJB, Wit H, Telang RS, Paramananthasivam V, Vlajkovic SM, Housley GD (2007) Regulation of the endocochlear potential by ATP in rodents: species differences. 7th IBRO World Congress of Neuroscience, Melbourne, Australia

  48. Housley GD, Kanjhan R, Raybould NP, Greenwood D, Salih SG, Jarlebark L, Burton LD, Setz VCM, Cannell MB, Soeller C, Christie DL, S-i U, Matsubara A, Yoshie H, Ryan AF, Thorne PR (1999) Expression of the P2X2 receptor subunit of the ATP-gated ion channel in the cochlea: implications for sound transduction and auditory neurotransmission. J Neurosci 19:8377–8388

    CAS  PubMed  Google Scholar 

  49. Vlajkovic SM, Thorne PR, Housley GD, Munoz DJ, Kendrick IS (1998) Ecto-nucleotidases terminate purinergic signalling in the cochlear endolymphatic compartment. NeuroReport 9:1559–1565

    CAS  PubMed  Google Scholar 

  50. O’Keeffe MG, Thorne PR, Housley GD, Robson SC, Vlajkovic SM (2010) Distribution of NTPDase5 and NTPDase6 and the regulation of P2Y receptor signalling in the rat cochlea. Purinergic Signaling. doi:10.1007/s11302-010-9190-y

  51. Vlajkovic SM, Housley GD, Munoz DJ, Robson SC, Sevigny J, Wang CJ, Thorne PR (2004) Noise exposure induces up-regulation of ecto-nucleoside triphosphate diphosphohydrolases 1 and 2 in rat cochlea. Neuroscience 126:763–773

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by grants from the Deafness Research Foundation and Auckland Medical Research Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter R. Thorne.

Additional information

Ravindra S. Telang and Vinthiya Paramananthasivam contributed equally to the work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Telang, R.S., Paramananthasivam, V., Vlajkovic, S.M. et al. Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea. Purinergic Signalling 6, 263–272 (2010). https://doi.org/10.1007/s11302-010-9195-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11302-010-9195-6

Keywords

Navigation