Measurement of the pH of the Endolymph in the Cochlea of Guinea Pigs

Misrahy, G. A.; Hildreth, Kenneth M.; Clark, Leland C.; Shinabarger, Edward W.

doi:10.1152/ajplegacy.1958.194.2.393

Cited by 27 publications

(13 citation statements)

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“…Desensitisation of ATP-gated currents has previously been described in DCs [Chen and Bobbin, 1998] from the guinea-pig organ of Corti. Despite high levels of Zn 2+ and Cu 2+ in the cochlear fluids (table 1) and the dynamics of cochlear pH [Mishrahy et al, 1958;Salt and Konishi, 1986;Hara et al, 1992Hara et al, , 1995Wangemann and Schacht, 1996], there is cur- Concentrations (in mM ) of divalent cations and pH value of the guinea-pig cochlear endolymph, perilymph (scala tympani) and cerebrospinal fluid (CSF). Total volume of cochlear endolymph and perilymph in the guinea-pig is approximately 2 and 16 Ìl respectively.…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore likely that acidification of the endolymph, and the presence of Cu 2+ , modulate the ATPactivated shunt conductance across the cochlear partition, mediated by the P2X receptors when endolymphatic ATP levels are elevated. Pathological conditions such as ischemia and hypoxia are associated with acidification [Mishrahy et al, 1958;Salt and Konishi, 1986;Wangemann and Schacht, 1996] and, along with exposure to loud noise, are likely to produce an increase in endolymphatic ATP levels [Muñoz et al, 2001].…”

Section: Modulation and Desensitisation Of Atp-gated Ion Channelsmentioning

confidence: 99%

“…The pH of the guinea-pig cochlear perilymph and the endolymph are approximately 7.4 (table 1) [Mishrahy et al, 1958;Salt and Konishi, 1986;Wangemann and Schacht, 1996]. The acidity of these fluids in situ appears to be very sensitive to changes in CO 2 tension and can fall to pH values of 6.8-7.0 under certain pathological conditions, such as ischemia and hypoxia [Mishrahy et al, 1958;Salt and Konishi, 1986;Wangemann and Schacht, 1996].…”

Section: Modulation Of Atp-gated Ion Channels By Extracellular Protonsmentioning

confidence: 99%

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Allosteric Modulation of Native Cochlear P2X Receptors: Insights from Comparison with Recombinant P2X<sub>2</sub> Receptors

Kanjhan

Raybould²,

Jagger³

et al. 2003

Audiol Neurotol

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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 Cu²⁺, but not Zn²⁺, enhanced the P2X receptor-mediated inward currents. Acid pH (6.5) potentiated OHC ATP-gated currents by 45%. Co-application of Cu²⁺ (1–40 µM) with ATP increased the response by 20%. In DCs, ATP-gated currents were potentiated 85% by acid pH, and 70% by Cu²⁺. Alkaline pH inhibited ATP-gated inward currents by 73% in OHCs and 85% in DCs. Zn²⁺ was either ineffective (1–10 µM) or inhibitory (40–400 µM). Recombinant rat P2X₂ receptor-mediated inward currents in Xenopus oocytes displayed allosteric modulation that was different from the native guinea-pig cochlear P2X receptors. The oocyte ATP-gated inward current was potentiated 450% by shifting from pH 7.5 to pH 6.5, and 130% with 40 µM Cu²⁺. The enhanced response to ATP with acid pH and Cu²⁺ is a signature of the P2X₂ subunit. In contrast to native guinea-pig cochlear cells, extracellular Zn²⁺ (40 µM) increased the recombinant ATP-gated inward current by 200% in oocytes. These results suggest that the positive allosteric modulation of cochlear OHC and DC ATP-gated ion channels by protons and Cu²⁺ arises in part from the P2X₂ receptor subunit, with additional regulatory elements.

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Section: Discussionmentioning

confidence: 99%

Section: Modulation and Desensitisation Of Atp-gated Ion Channelsmentioning

confidence: 99%

Section: Modulation Of Atp-gated Ion Channels By Extracellular Protonsmentioning

confidence: 99%

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Allosteric Modulation of Native Cochlear P2X Receptors: Insights from Comparison with Recombinant P2X<sub>2</sub> Receptors

Kanjhan

Raybould²,

Jagger³

et al. 2003

Audiol Neurotol

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“…It has also been reported that the chloride concentration (3) and pH (4) ( to implicate these ions in the genesis of the EP. Two possibilities for this relationship include a sodium diffusion potential or an inwardly directed electrogenic potassium pump (5).…”

Section: Introductionmentioning

confidence: 93%

The Mutual Independence of the Endolymphatic Potential and the Concentrations of Sodium and Potassium in Endolymph

Brusilow¹,

Gordes²

1973

J. Clin. Invest.

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A B S T R A C T The relationship between the endolymphatic potential (EP) and the sodium and potassium concentration gradients between endolymph and interstitial fluid was studied both by measuring the EP at varying concentrations of sodium and potassium in endolymph and by measuring the effect of a depressed EP on the concentrations of these cations. Ethacrynic acid was used in dogs to change the concentration of sodium and potassium (meq/liter) in endolymph from 5.8 and 148 to 134 and 24.3, respectively. No change in the EP accompanied these alterations. In a second series of experiments the EP was reduced from + 72 mV to + 31 mV for a mean duration of 20 min. No change in the concentration of sodium and potassium in endolymph was found during the period of reduced EP. These data suggest that there is little relationship between the EP and the sodium and potassium concentrations in endolymph. INTRODUCTIONVon Bekesy (1) discovered that the endolymphatic potential (EP) 1 is + 75 mV and Smith, Lowry, and Wu (2) showed that the potassium concentration in endolymph is approximately 150 meq/liter and the sodium concentration is less than 20 meq/liter. It has also been reported that the chloride concentration (3) and pH

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“…This observation may suggest that the extracellular solution in IS or in the ligament may not be acidic enough, because omeprazole is activated only in a strong acidic environment of pH Ͻ5 (51, 89). Actually, it has been reported that pH of perilymph is 7.8 -8.0 (56). This may be due to the effective neutralization of the protons by HCO 3 Ϫ secreted via Cl Ϫ /HCO 3 Ϫ exchangers expressed in the outer sulcus cells neighboring the fibrocytes (75).…”

Section: C1045mentioning

confidence: 99%

Gastric type H⁺,K⁺-ATPase in the cochlear lateral wall is critically involved in formation of the endocochlear potential

Shibata

Hibino²,

Doi³

et al. 2006

American Journal of Physiology-Cell Physiology

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Cochlear endolymph has a highly positive potential of approximately +80 mV known as the endocochlear potential (EP). The EP is essential for hearing and is maintained by K+ circulation from perilymph to endolymph through the cochlear lateral wall. Various K+ transport apparatuses such as the Na+,K+-ATPase, the Na+-K+-2Cl− cotransporter, and the K+ channels Kir4.1 and KCNQ1/KCNE1 are expressed in the lateral wall and are known to play indispensable roles in cochlear K+ circulation. The gastric type of the H+,K+-ATPase was also shown to be expressed in the cochlear lateral wall (Lecain E, Robert JC, Thomas A, and Tran Ba Huy P. Hear Res 149: 147–154, 2000), but its functional role has not been well studied. In this study we examined the precise localization of H+,K+-ATPase in the cochlea and its involvement in formation of EP. RT-PCR analysis showed that the cochlea expressed mRNAs of gastric α1-, but not colonic α2-, and β-subunits of H+,K+-ATPase. Immunolabeling of an antibody specific to the α1 subunit was detected in type II, IV, and V fibrocytes distributed in the spiral ligament of the lateral wall and in the spiral limbus. Strong immunoreactivity was also found in the stria vascularis. Immunoelectron microscopic examination exhibited that the H+,K+-ATPase was localized exclusively at the basolateral site of strial marginal cells. Application of Sch-28080, a specific inhibitor of gastric H+,K+-ATPase, to the spiral ligament as well as to the stria vascularis caused prominent reduction of EP. These results may imply that the H+,K+-ATPase in the cochlear lateral wall is crucial for K+ circulation and thus plays a critical role in generation of EP.

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Measurement of the pH of the Endolymph in the Cochlea of Guinea Pigs

Cited by 27 publications

References 0 publications

Allosteric Modulation of Native Cochlear P2X Receptors: Insights from Comparison with Recombinant P2X<sub>2</sub> Receptors

Allosteric Modulation of Native Cochlear P2X Receptors: Insights from Comparison with Recombinant P2X<sub>2</sub> Receptors

The Mutual Independence of the Endolymphatic Potential and the Concentrations of Sodium and Potassium in Endolymph

Gastric type H⁺,K⁺-ATPase in the cochlear lateral wall is critically involved in formation of the endocochlear potential

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Measurement of the pH of the Endolymph in the Cochlea of Guinea Pigs

Cited by 27 publications

References 0 publications

Allosteric Modulation of Native Cochlear P2X Receptors: Insights from Comparison with Recombinant P2X<sub>2</sub> Receptors

Allosteric Modulation of Native Cochlear P2X Receptors: Insights from Comparison with Recombinant P2X<sub>2</sub> Receptors

The Mutual Independence of the Endolymphatic Potential and the Concentrations of Sodium and Potassium in Endolymph

Gastric type H+,K+-ATPase in the cochlear lateral wall is critically involved in formation of the endocochlear potential

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Product

Resources

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Gastric type H⁺,K⁺-ATPase in the cochlear lateral wall is critically involved in formation of the endocochlear potential