title: Purinergic regulation of sound transduction and auditory neurotransmission.
abstract: In the cochlea, extracellular ATP influences the endocochlear potential, micromechanics, and neurotransmission via P2 receptors. Evidence for this arises from studies demonstrating widespread expression of ATP-gated ion channels (assembled from P2X receptor subunits) and G protein-coupled receptors (P2Y receptors). P2X2 receptor subunits are localized to the luminal membranes of epithelial cells and hair cells lining scala media. These ion channels provide a shunt pathway for K+ ion egress. Thus, when noise exposure elevates ATP levels in this cochlear compartment, the K+ conductance through P2X receptors reduces the endocochlear potential. ATP-mediated K+ efflux from scala media is complemented by a P2Y receptor G protein-coupled pathway that provides coincident reduction of K+ transport into scala media from the stria vascularis when autocrine or paracrine ATP signalling is invoked. This purinergic signalling likely provides a basis for a reactive homoeostatic regulatory mechanism limiting cochlear sensitivity under stressor conditions. Elevation of ATP in the perilymphatic compartment under such conditions is also likely to invoke purinergic receptor-mediated changes in supporting cell micromechanics, mediated by Ca2+ influx and gating of Ca2+ stores. Independent of these humoral actions, ATP can be classified as a putative auditory neurotransmitter based on the localization of P2X receptors at the spiral ganglion neuron-hair cell synapse, and functional verification of ATP-gated currents in spiral ganglion neurons in situ. Expression of P2X receptors by type II spiral ganglion neurons supports a role for ATP as a transmitter encoding the dynamic state of the cochlear amplifier.
authors.affiliation: Physiology Division, Faculty of Medicine and Health Sciences, University of Auckland, New Zealand.
authors.forename: G D
authors.initials: GD
authors.lastname: Housley
authors.forename: D J
authors.initials: DJ
authors.lastname: Jagger
authors.forename: D
authors.initials: D
authors.lastname: Greenwood
authors.forename: N P
authors.initials: NP
authors.lastname: Raybould
authors.forename: S G
authors.initials: SG
authors.lastname: Salih
authors.forename: L E
authors.initials: LE
authors.lastname: Järlebark
authors.forename: S M
authors.initials: SM
authors.lastname: Vlajkovic
authors.forename: R
authors.initials: R
authors.lastname: Kanjhan
authors.forename: P
authors.initials: P
authors.lastname: Nikolic
authors.forename: D J M
authors.initials: DJ
authors.lastname: Muñoz
authors.forename: P R
authors.initials: PR
authors.lastname: Thorne
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D003051:Cochlea / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000502:physiology; D006309:Hearing / Q000502:physiology*; D006801:Humans; D009475:Neurons, Afferent / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013136:Spiral Ganglion / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate