The auditory nerve transmits acoustic signals from cochlear hair cells to the brain. The spiral ganglion neurons (SGNs) that form the primary afferent pathway are reliant on glial cells for their function and long-term survival, but neuro-glial interactions remain largely uncharacterized. Purinergic signaling is recognized as a regulator of auditory nerve physiology, following the detection of various P2X and P2Y receptors, and demonstration of neuronal ionotropic and metabotropic responses (Housley et al, 2002). Here, we examined P2X7 receptors (P2X7Rs) as potential mediators of neuro-glial communication in the cochlea. In rat cochlear vibratome sections, P2X7R immunofluorescence was first detected at postnatal day 6 (P6) in Schwann cells wrapping SGN peripheral neurites and in satellite cells surrounding the SGN cell bodies, but not in oligodendrocytes in the central portion of the auditory nerve. This expression pattern was conserved through to adulthood. Elsewhere in the peripheral nervous system P2X7Rs are non-selectively permeable to small cations when stimulated transiently, but during prolonged agonist exposure there is an increased permeability to larger cationic molecules up to 1kDa (e.g. fluorescent dyes). To confirm functional expression and investigate the properties of P2X7Rs in cochlear glia, we prepared dissociated spiral ganglion cultures from hearing rats (P13-P14). In electrophysiology and dye uptake experiments P2X7Rs were stimulated using the P2X agonist BzATP (10 µM) and blocked by the specific P2X7R antagonist A-740003 (100 nM). Patch clamp recordings demonstrated BzATP-activated currents that increased in magnitude with prolonged exposure time, and that were inhibited by A-740003. BzATP activated rapid YOPRO-1 uptake into glia during time series confocal imaging, and the YOPRO-1 uptake was prevented by incubation with A-740003. Where an SGN and its satellite cell remained paired, BzATP-mediated YOPRO-1 uptake could be detected only within the satellite cell. The present study demonstrates functional expression of P2X7Rs in glial cells within the peripheral portion of the auditory nerve, raising the possibility that these enigmatic ion channels play roles in cochlear neuro-glial communication. We suggest that P2XRs may act as sensors of tissue stress during periods of damaging noise or ischemia.