Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea |
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Authors: | Ravindra S. Telang Vinthiya Paramananthasivam Srdjan M. Vlajkovic David J. B. Munoz Gary D. Housley Peter R. Thorne |
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Affiliation: | (1) Discipline of Audiology, The University of Auckland, Auckland, New Zealand;(2) Department of Physiology, The University of Auckland, Auckland, New Zealand;(3) Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia;(4) Section of Audiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; |
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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. |
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Keywords: | Ageing Noise Endocochlear potential Auditory brainstem response CBA/CaJ Immunohistochemistry P2X2 receptors |
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