Differential expression of purinergic receptor subtypes in the outer hair cells of the guinea pig

Szűcs, Attila; Szappanos, Henrietta Cserné; Tóth, Andrea; Farkas, Zsolt; Panyi, György; Csernoch, László; Sziklai, István

doi:10.1016/j.heares.2004.04.008

Cited by 30 publications

(32 citation statements)

References 28 publications

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“…S1), indicating that ATP sinks K + through the activation of the P2X receptors. Multiple expression of P2X isoforms have been identified in the cochlea, including supporting cells [18,20,21,23,29,30]. P2X2, P2X4, and P2X7 are the predominant isoforms.…”

Section: Discussionmentioning

confidence: 99%

“…P2 receptors have two subgroups: ATP-gated ionotropic (P2X) receptors and G-protein-coupled metabotropic (P2Y) receptors. Both P2X and P2Y receptors are expressed in the cochlea, including supporting cells [16][17][18][19][20][21][22][23]. Recently, we have demonstrated that gap junctional hemichannels in the cochlear supporting cells can release ATP [24], which can activate P2x receptors in the outer hair cells (OHCs) to induce Ca ++ influx and modulate OHC electromotility [24,25].…”

Section: Introductionmentioning

confidence: 99%

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ATP-mediated potassium recycling in the cochlear supporting cells

Zhu

Zhao

2010

Purinergic Signalling

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Gap junction-mediated K + recycling in the cochlear supporting cell has been proposed to play a critical role in hearing. However, how potassium ions enter into the supporting cells to recycle K + remains undetermined. In this paper, we report that ATP can mediate K + sinking to recycle K + in the cochlear supporting cells. We found that micromolar or submicromolar levels of ATP could evoke a K + -dependent inward current in the cochlear supporting cells. At negative membrane potentials and the resting membrane potential of −80 mV, the amplitude of the ATPevoked inward current demonstrated a linear relationship to the extracellular concentration of K + , increasing as the extracellular concentration of K + increased. The inward current also increased as the concentration of ATP was increased. In the absence of ATP, there was no evoked inward current for extracellular K + challenge in the cochlear supporting cells. The ATP-evoked inward current could be inhibited by ionotropic purinergic (P2X) receptor antagonists. Application of pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS, 50 µM) or pre-incubation with an irreversible P2X7 antagonist oxidized ATP (oATP, 0.1 mM) completely abolished the ATP-evoked inward current at the negative membrane potential. ATP also evoked an inward current at cell depolarization, which could be inhibited by intracellular Cs + and eliminated by positive holding potentials. Our data indicate that ATP can activate P2X receptors to recycle K + in the cochlear supporting cells at the resting membrane potential under normal physiological and pathological conditions. This ATP-mediated K + recycling may play an important role in the maintenance of cochlear ionic homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ATP-mediated potassium recycling in the cochlear supporting cells

Zhu

Zhao

2010

Purinergic Signalling

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“…HCs express both P2X and P2Y receptors (Housley et al 1992;Housley et al 1998;Housley et al 1999;Szücs et al 2004;Huang et al 2010). We investigated whether these receptors are required for phalloidin entry through hair cells using PPADs and suramin, non-selective P2 antagonists (Lambrecht et al 1992;Li 2000;Surprenant et al 2000;Lambrecht et al 2002;North 2002;Trujillo et al 2006).…”

Section: Fig 3 Hair Cell Density Was Not Affected In Phalloidin-trementioning

confidence: 99%

Permeation of Fluorophore-Conjugated Phalloidin into Live Hair Cells of the Inner Ear Is Modulated by P2Y Receptors

Thiede

Corwin

2013

JARO

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Phalloidin, a toxin isolated from the death cap mushroom, Amanita phalloides, binds to filamentous actin with high affinity, and this has made fluorophore-conjugated phalloidin a useful tool in cellular imaging. Hepatocytes take up phalloidin via the liver-specific organic anion transporting polypeptide 1b2, but phalloidin does not permeate most living cells. Rapid entry of styryl dyes into live hair cells has been used to evaluate function, but the usefulness of those fluorescence dyes is limited by broad and fixed absorption spectra. Since phalloidin can be conjugated to fluorophores with various spectra, we investigated whether it would permeate living hair cells. When we incubated mouse utricles in 66 nM phalloidin-CF488A and followed that by washes in phalloidin-free medium, we observed that it entered a subset of hair cells and labeled entire hair bundles fluorescently after 20 min. Incubations of 90 min labeled nearly all the hair bundles. When phalloidin-treated utricles were cultured for 24 h after washout, the label disappeared from the hair cells and progressively but heterogeneously labeled filamentous actin in the supporting cells. We investigated how phalloidin may enter hair cells and found that P2 receptor antagonists, pyridoxalphosphate-6-azophenyl-2′, 4′-disulfonic acid and suramin, blocked phalloidin entry, while the P2Y receptor ligands, uridine-5'-diphosphate and uridine-5'-triphosphaste, stimulated uptake. Consistent with that, the P2Y6 receptor antagonist, MRS 2578, decreased phalloidin uptake. The results show that phalloidin permeates live hair cells through a pathway that requires metabotropic P2Y receptor signaling and suggest that phalloidin can be transferred from hair cells to supporting cells in culture.

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“…OHCs have predominant expressions of P2x2 and P2x7 receptors [10,16,[21][22][23]; they also have P2y2 and P2y4 expressions [23,24,30] but have no P2y1 and P2y12 expressions [30]. It has been proposed that P2y receptors may be involved in setting the operating point of OHC transduction [31].…”

Section: Atp Modifies Ohc Electromotility Through the Activation Of Pmentioning

confidence: 99%

“…Each subgroup has several subtypes [17,18]. OHCs have both P2x and P2y expressions [10,16,[19][20][21][22][23][24]. In this study, the P2 receptor activity and ionic dependence underlying the effect of ATP on OHC electromotility were studied.…”

Section: Introductionmentioning

confidence: 99%

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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Differential expression of purinergic receptor subtypes in the outer hair cells of the guinea pig

Cited by 30 publications

References 28 publications

ATP-mediated potassium recycling in the cochlear supporting cells

ATP-mediated potassium recycling in the cochlear supporting cells

Permeation of Fluorophore-Conjugated Phalloidin into Live Hair Cells of the Inner Ear Is Modulated by P2Y Receptors

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

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