title: Expression of the P2X(2) receptor subunit of the ATP-gated ion channel in the cochlea: implications for sound transduction and auditory neurotransmission.
abstract: Extracellular ATP has multimodal actions in the cochlea affecting hearing sensitivity. ATP-gated ion channels involved in this process were characterized in the guinea pig cochlea. Voltage-clamped hair cells exhibited a P2 receptor pharmacology compatible with the assembly of ATP-gated ion channels from P2X(2) receptor subunits. Reverse transcription-PCR experiments confirmed expression of the P2X(2-1) receptor subunit mRNA isoform in the sensory epithelium (organ of Corti); a splice variant that confers desensitization, P2X(2-2), was the predominant subunit isoform expressed by primary auditory neurons. Expression of the ATP-gated ion channel protein was localized using a P2X(2) receptor subunit-specific antiserum. The highest density of P2X(2) subunit-like immunoreactivity in the cochlea occurred on the hair cell stereocilia, which faces the endolymph. Tissues lining this compartment exhibited significant P2X(2) receptor subunit expression, with the exception of the stria vascularis. Expression of ATP-gated ion channels at these sites provides a pathway for the observed ATP-induced reduction in endocochlear potential and likely serves a protective role, decoupling the "cochlear amplifier" in response to stressors, such as noise and ischemia. Within the perilymphatic compartment, immunolabeling on Deiters' cells is compatible with purinergic modulation of cochlear micromechanics. P2X(2) receptor subunit expression was also detected in spiral ganglion primary afferent neurons, and immunoelectron microscopy localized these subunits to postsynaptic junctions at both inner and outer hair cells. The former supports a cotransmitter role for ATP in a subset of type I spiral ganglion neurons, and latter represents the first characterization of a receptor for a fast neurotransmitter associated with the type II spiral ganglion neurons.
authors.affiliation: Department of Physiology, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: G D
authors.initials: GD
authors.lastname: Housley
authors.forename: R
authors.initials: R
authors.lastname: Kanjhan
authors.forename: N P
authors.initials: NP
authors.lastname: Raybould
authors.forename: D
authors.initials: D
authors.lastname: Greenwood
authors.forename: S G
authors.initials: SG
authors.lastname: Salih
authors.forename: L
authors.initials: L
authors.lastname: Järlebark
authors.forename: L D
authors.initials: LD
authors.lastname: Burton
authors.forename: V C
authors.initials: VC
authors.lastname: Setz
authors.forename: M B
authors.initials: MB
authors.lastname: Cannell
authors.forename: C
authors.initials: C
authors.lastname: Soeller
authors.forename: D L
authors.initials: DL
authors.lastname: Christie
authors.forename: S
authors.initials: S
authors.lastname: Usami
authors.forename: A
authors.initials: A
authors.lastname: Matsubara
authors.forename: H
authors.initials: H
authors.lastname: Yoshie
authors.forename: A F
authors.initials: AF
authors.lastname: Ryan
authors.forename: P R
authors.initials: PR
authors.lastname: Thorne
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D002923:Cilia / Q000502:physiology / Q000648:ultrastructure; D003051:Cochlea / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000502:physiology; D006309:Hearing / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008297:Male; D009925:Organ of Corti / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D058476:Receptors, Purinergic P2X2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D007473:Ion Channels; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D000255:Adenosine Triphosphate