Extracellular adenosine 5′-triphosphate (ATP) in the endolymphatic compartment influences cochlear function

Munoz, D. J. B.; Thorne, Peter R.; Housley, Gary D.; Billett, Tania E.; Battersby, James M.

doi:10.1016/0378-5955(95)00152-3

Cited by 74 publications

(41 citation statements)

References 32 publications

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“…4). It has long been known that the cochlear PL and EL contain nanomolar concentrations of ATP that can mediate cochlear and hearing functions (26,(30)(31)(32). However, the origin of the intracochlear ATP and the mechanism of its effects remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear

Zhao

Yu²,

Fleming³

2005

Proc. Natl. Acad. Sci. U.S.A.

182

221

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Connexin gap junctions play an important role in hearing function, but the mechanism by which this contribution occurs is unknown. Connexins in the cochlea are expressed only in supporting cells; no connexin expression occurs in auditory sensory hair cells. A gap junctional channel is formed by two hemichannels. Here, we show that connexin hemichannels in the cochlea can release ATP at levels that account for the submicromolar concentrations measured in the cochlear fluids in vivo. The release could be increased 3-to 5-fold by a reduction of extracellular Ca 2؉ or an increase in membrane stress, and blocked by gap junctional blockers. We also demonstrated that extracellular ATP at submicromolar levels apparently affected outer hair cell (OHC) electromotility, which is an active cochlear amplifier determining cochlear sensitivity to sound stimulation in mammals. ATP reduced OHC electromotility and the slope factor of the voltage dependence and shifted the operating point to reduce the active amplifier gain. ATP also reduced the generation of distortion products. Immunofluorescent staining showed that purinergic receptors P2x2 and P2x7 were distributed on the OHC surface. Blockage of P2 receptors eliminated the effect of ATP on the OHC electromotility. The data revealed that there is a hemichannel-mediated, purinergic intercellular signaling pathway between supporting cells and hair cells in the cochlea to control hearing sensitivity. The data also demonstrated a potential source of ATP in the cochlea.active cochlear mechanics ͉ cochlear supporting cells ͉ connexin ͉ outer hair cell electromotility ͉ P2 receptor

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Section: Discussionmentioning

confidence: 99%

Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear

Zhao

Yu²,

Fleming³

2005

Proc. Natl. Acad. Sci. U.S.A.

182

221

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“…Further, they found that when ATP is injected into scala media it causes a rapid and reversible fall in the endocochlear potential and a concomitant decrease in hearing sensitivity (increase in compound action potential thresholds) (Munoz et al, 1999;Munoz et al, 1995). They recently have shown that this ATP-induced fall in endocochlear potential can be attributed to a shunt across the cochlear partition (measured as a fall in cochlear partition resistance) arising from a cation (principally K + ) flux through ATP-gated ion channels (P2X receptors) present on the endolymphatic surface of epithelial cells lining scala media .…”

Section: Apical (Endolymphatic Side) Receptorsmentioning

confidence: 99%

Purinergic signaling in the inner ear

Lee

Marcus

2008

Hearing Research

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Epithelial cells of the inner ear coordinate their ion transport activity through a number of mechanisms. One important mechanism is the autocrine and paracrine signaling among neighboring cells in the ear via nucleotides, such as adenosine, ATP and UTP. This review summarizes observations on the release, detection and degradation of nucleotides by epithelial cells of the inner ear. Purinergic signaling is thought to be important for endolymph ion homeostasis and for protection from over stimulation.

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“…These changes can reduce the gain of the cochlear amplifier to decrease hearing sensitivity. It has been found that intracochlear perfusion of ATP could reduce both the endocochlear potential (EP) and CM [3]. The intracochlear perfusion of ATP also decreased DPOAEs [2,3].…”

Section: Possible Mechanisms Of Atp Regulation In Hearing Functionmentioning

confidence: 99%

“…It has been found that intracochlear perfusion of ATP could reduce both the endocochlear potential (EP) and CM [3]. The intracochlear perfusion of ATP also decreased DPOAEs [2,3]. These proposed changes resulted from shifting the operating point of the cochlear amplifier to reduce the amplifier gain [31].…”

Section: Possible Mechanisms Of Atp Regulation In Hearing Functionmentioning

confidence: 99%

“…An early experiment demonstrated that the application of ATP to the perilymph in the guinea pig cochlea affected auditory nerve activity [1]. Intracochlear perfusion of ATP also reduced the cochlear microphonics (CM) and the compound action potential [2][3][4][5]. It has been reported that ATP can evoke inward currents and raise the intracellular Ca ++ concentration in cochlear outer and inner hair cells, thereby modifying sound transduction and neurotransmission [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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ATP activates P2x receptors and requires extracellular Ca++ participation to modify outer hair cell nonlinear capacitance

Zhao

2008

Pflugers Arch - Eur J Physiol

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Intracochlear ATP is an important mediator in regulating hearing function. ATP can activate ionotropic purinergic (P2x) and metabotropic purinergic (P2y) receptors to influence cell functions. In this paper, we report that ATP can activate P2x receptors directly to modify outer hair cell (OHC) electromotility, which is an active cochlear amplifier determining hearing sensitivity and frequency selectivity in mammals. We found that ATP, but not UTP, a P2y receptor agonist, reduced the OHC electromotility-associated nonlinear capacitance (NLC) and shifted its voltage dependence to the right (depolarizing) direction. Blockage of the activation of P2x receptors by pyridox-alphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), suramin, and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) could block the ATP effect. This modification also required extracellular Ca ++ participation. Removal of extracellular Ca ++ abolished the ATP effect. However, chelation of intracellular Ca ++ concentration by a fast calciumchelating reagent 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA, 10 mM) did not affect the effect of ATP on NLC. The effect is also independent of K + ions. Substitution of Cs + for intracellular or extracellular K + did not affect the ATP effect. Our findings indicate that ATP activates P2x receptors instead of P2y receptors to modify OHC electromotility. Extracellular Ca ++ is required for this modification.

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Extracellular adenosine 5′-triphosphate (ATP) in the endolymphatic compartment influences cochlear function

Cited by 74 publications

References 32 publications

Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear

Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear

Purinergic signaling in the inner ear

ATP activates P2x receptors and requires extracellular Ca++ participation to modify outer hair cell nonlinear capacitance

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