Noise-induced up-regulation of NTPDase3 expression in the rat cochlea: Implications for auditory transmission and cochlear protection

Stimuli such as noise or hypoxia can induce a release of ATP into the cochlear fluid spaces. At nanomolar concentrations, ATP affects neurotransmission and electrochemical regulation of sound transduction. At higher concentrations, ATP may exert cytotoxicity acting on specific P2X7 receptor subunits, thus contributing to the pathophysiology of noise-induced cochlear injury. Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are pivotal to regulation of extracellular nucleotide concentrations and therefore P2 receptor signaling in the cochlea. Here, we characterize the distribution of NTPDase3 ectonucleotidase (preferentially hydrolyzes ATP over ADP) in cochlear tissues and investigate the effect of noise exposure on NTPDase3 expression. Marked NTPDase3 immunoreactivity in the primary afferent neurones of the spiral ganglion, extending in the distal neurite processes to the synapses beneath the inner and outer hair cells, suggests involvement in auditory neurotransmission. Immunolabeling in the lateral wall and epithelial cells lining the cochlear partition was also evident. Semi-quantitative immunohistochemistry revealed increased NTPDase3 immunolabeling in the synaptic regions of the inner and outer hair cells at sound intensities that induce temporary threshold shift. The results suggest a role for NTPDase3 in regulating ATP signaling associated primarily with auditory neurotransmission, and the potential neuroprotective nature of noise-induced up-regulation of this ectonucleotidase in the cochlea.