Previously published evidence is reviewed for a functional role of ATP and its receptors at the chemical synapse between the mammalian inner hair cell and the primary afferent dendrites of the VIIIth nerve. New findings are also presented, both from gross cochlear potentials and single neurone recordings during intracochlear perfusion of ATP-receptor antagonists and agonists. Both the previous and present results are consistent with the notion that endogenous ATP may act to regulate the excitability of the primary afferent dendrite, possibly acting on P2X2 receptors.

Keywords:
Suramin, PPADS, Adenosine 5′-triphosphate analogues, Purinergic receptors, Compound action potential, Summating potential, Single afferent neurons, Spiral ganglion, Spontaneous activity, Tuning curves
1.
Brandle U, Zenner HP, Ruppersberg JP: Gene expression of P2X-receptors in the developing inner ear of the rat. Neurosci Lett 1999;273:105–108.
2.
Burnstock G: Purinergic co-transmission. Brain Res Bull 1999;50:355–357.
3.
Chen C, Parker MS, Barnes AP, Deininger P, Bobbin RP: Functional expression of three P2X(2) receptor splice variants from guinea pig cochlea. J Neurophysiol 2000;83:1502–1509.
4.
Chen C, Skellet RA, Fallon M, Bobbin RP: Additional pharmacological evidence that endogenous ATP modulates cochlear mechanics. Hear Res 1998;118:47–61.
5.
Housley GD: Extracellular nucleotide signaling in the inner ear. Mol Neurobiol 1998;16:21–48.
6.
Housley GD: Physiological effects of extracellular nucleotides in the inner ear. Clin Exp Pharmacol Physiol 2000;27:575–580.
7.
Housley GD, Kanjhan R, Raybould NP, Greenwood D, Salih SG, Jarlebark L, Burton LD, Setz VC, Cannell MB, Soeller C, Christie DL, Usami S, Matsubara A, Yoshie H, Ryan AF, Thorne PR: Expression of the P2X(2) receptor subunit of the ATP-gated ion channel in the cochlea: Implications for sound transduction and auditory neurotransmission. J Neurosci 1999;19:8377–8388.
8.
Housley GD, Luo L, Ryan AF: Localization of mRNA encoding the P2X2 receptor subunit of the adenosine 5′-triphosphate-gated ion channel in the adult and developing rat inner ear by in situ hybridization. J Comp Neurol 1998;393:403–414.
9.
Jagger D, Robertson D, Housley GD: A technique for slicing the rat cochlea around the onset of hearing. J Neurosci Meth 2000;104:77–86.
10.
Jarlebark LE, Housley GD, Thorne PR: Immunohistochemical localization of adenosine 5′-triphosphate-gated ion channel P2X(2) receptor subunits in adult and developing rat cochlea. J Comp Neurol 2000;421:289–301.
11.
King M, Housley GD, Raybould NP, Greenwood D, Salih SG: Expression of ATP-gated ion channels by Reissner’s membrane epithelial cells. Neuroreport 1998;9:2467–2474.
12.
Kujawa SG, Erostegui C, Fallon M, Crist J, Bobbin RP: Effects of adenosine 5′-triphosphate and related agonists on cochlear function. Hear Res 1994a;76:87–100.
13.
Kujawa SG, Fallon M, Bobbin RP: ATP antagonists cibacron blue, basilen blue and suramin alter sound-evoked responses of the cochlea and auditory nerve. Hear Res 1994b;78:181–188.
14.
Lambrecht G: Agonists and antoagonists acting at P2X receptors: Selectivity profiles and functional implications. Naunyn-Schmiedeberg’s Arch Pharmacol 2000;362:340–350.
15.
Liberman MC: Single neuron labeling in the cat auditory nerve. Science 1982;216:1239–1241.
16.
Munoz DJ, Thorne PR, Housley GD: P2X receptor-mediated changes in cochlear potentials arising from exogenous adenosine 5′-triphosphate in endolymph. Hear Res 1999;138:56–64.
17.
Nikolic P, Housley GD, Luo L, Ryan AF, Thorne PR: Transient expression of P2X(1) receptor subunits of ATP-gated ion channels in the developing rat cochlea. Brain Res Dev Brain Res 2001;126:173–182.
18.
Robertson D: Horseradish peroxidase injection of physiologically characterized afferent and efferent neurons in the guinea pig spiral ganglion. Hear Res 1984;15:113–121.
19.
Robertson D, Johnstone BM: Effects of divalent cations on spontaneous and evoked activity of single mammalian auditory neurons. Pflugers Arch 1979;380:7–12.
20.
Ruel J, Chen C, Pujol R, Bobbin RP, Puel JL: AMPA-preferring glutamate receptors in cochlear physiology of adult guinea pig. J Physiol 1999;518:667–680.
21.
Salih SG, Housley GD, Burton LD, Greenwood D: P2X2 receptor subunit expression in a subpopulation of cochlear type I spiral ganglion neurons. Neuroreport 1998;9:279–282.
22.
Salih SG, Housley GD, Raybould NP, Thorne PR: ATP-gated ion channel expression in primary auditory neurons. Neuroreport 1999;10:2579–2586.
23.
Sugasawa M, Erostegui C, Blanchet C, Dulon D: ATP activates non-selective cation channels and calcium release in inner hair cells of the guinea-pig cochlea. J Physiol 1996;491:707–718.
24.
Winter IM, Robertson D, Yates GK: Diversity of characteristic rate-intensity functions in guinea pig auditory nerve fibres. Hear Res 1990;45:191–202.
25.
Zhang SY, Robertson D, Yates G, Everett A: Role of L-type Ca(2+) channels in transmitter release from mammalian inner hair cells. I. Gross sound-evoked potentials. J Neurophysiol 1999;82:3307–3315.
26.
Zimmerman H: Signalling via ATP in the nervous system. Trends Neurosci 1994;17:420–426.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.