Nicholas P. Raybould

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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(More)
Reissner's membrane forms a partition between the endolymphatic and perilymphatic cochlear compartments. Expression of the P2X2 receptor subunit which assembles to form ATP-gated ion channels was detected in guinea-pig Reissner's membrane using the reverse transcription polymerase chain reaction (RT-PCR). The P2X2 receptor subunit protein was localized to(More)
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(More)
Ca2+ signalling is central to cochlear sensory hair cell physiology through its influence on sound transduction, membrane filter properties and neurotransmission. However, the mechanism for establishing Ca2+ homeostasis in these cells remains unresolved. Canonical transient receptor potential (TRPC) Ca2+ entry channels provide an important pathway for(More)
In mammals, sound transduction by inner hair cells (IHC) generates a receptor potential whose amplitude and phase drive auditory nerve firing. The membrane filter properties that define the input-output function of IHC are derived from membrane conductance and capacitance. These elements of the membrane filter were quantified using whole-cell voltage clamp(More)
Extracellular ATP has several neuro-humoral actions on cochlear physiology, many of which involve P2X receptor-mediated signal transduction. The present study extends the molecular physiology of P2X receptor gene expression in the cochlea to the principal platform for transgenic studies, the mouse model. P2X receptor subunits, which assemble to form(More)
Regulation of P2X(2) receptor (P2X(2)R) expression in the rat cochlea in response to noise was analysed. Sustained loud sound (90-120 dB white noise, > 6 h), increased P2X(2)R mRNA and protein levels in rat organ of Corti and spiral ganglion (primary auditory neurones). P2X(2)R expression by the type I spiral ganglion neurones, which innervate the inner(More)
The adenosine 5'-triphosphate (ATP)-activated membrane conductance, mediated by P2X receptors, was examined in isolated guinea-pig cochlear inner and outer hair cells. Photo-activated release of caged-ATP elicted a 30-ms latency inwardly rectifying non-selective cation conductance, blocked by the P2X receptor antagonist(More)
Extracellular adenosine 5'-triphosphate (ATP)-gated ion channels assembled from P2X receptor subunits exhibit subunit-selective allosteric modulation by protons and divalent cations. In voltage-clamped guinea-pig cochlear outer hair cells (OHC) and Deiters' cells (DC), H(+) and Cu(2+), but not Zn(2+), enhanced the P2X receptor-mediated inward currents. Acid(More)
1. Whole-cell patch-clamp recordings were used to determine the variation in the P2X receptor conductance, activated by extracellular ATP, in outer hair cells (OHCs) isolated from each of the four turns of the guinea-pig cochlea. 2. In standard solution (containing 1.5 mM Ca2+) slope conductances were determined in OHCs of known origin from current-voltage(More)