Reduction of the Endocochlear Potential by the New “Loop” Diuretic, Bumetanide

Kusakari, Jun; Kambayashi, Jun-ichi; Ise, Ikuo; Kawamoto, Kazutomo

doi:10.3109/00016487809124755

Cited by 37 publications

(6 citation statements)

References 24 publications

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“…Conversely, SLC12A2 deficiency, as discussed above, leads to deafness without leading to overt renal salt wasting (43,57). Importantly, both SLC12A1 and SLC12A2 are inhibited by loop diuretics such as furosemide, and thus inhibition of Na ϩ -2Cl Ϫ -K ϩ cotransport in the inner ear during excessive doses of loop diuretics leads to an accumulation of K ϩ in the intrastrial space, which abolishes the endocochlear potential (129) and leads to hearing loss (81,96,322). Much lower doses are sufficient to inhibit luminal SLC12A1 in the thick ascending limb, since the drug accumulates in the tubular fluid as a consequence of efficient secretion into proximal tubular fluid and fluid reabsorption along the tubule.…”

Section: Functions Of Inner Ear Channels and Transporters In Renal Epmentioning

confidence: 96%

“…The Na ϩ /K ϩ -ATPase in strial marginal cells and vestibular dark cells as well as in fibrocytes of the spiral ligament consists of the subunits ATP1A1, ATP1B1, and ATP1B2 (173,230) (Fig. 2D) Inhibition of Na ϩ /K ϩ -ATPase with ouabain inhibits K ϩ secretion and consequently abolishes the endocochlear potential (126,129). Strial marginal cells appear to express gastric K ϩ /H ϩ -ATPase in addition to Na ϩ /K ϩ -ATPase (135,235).…”

Section: K ϩ Cycling In the Inner Earmentioning

confidence: 98%

“…Fifth, increases of the K ϩ concentration in the intrastrial fluid space suppress the endocochlear potential. Such increases can be achieved by vascular perfusion of solutions containing elevated K ϩ concentrations, inhibitors of Na ϩ /K ϩ -ATPase (ouabain), or inhibitors of the Na ϩ -2Cl Ϫ -K ϩ cotransporter (furosemide or bumetanide) (118,126,128,129,164). Finally, loss of GJB6 [connexin (Cx)30], which renders capillaries in the stria vascularis leaky to the intrastrial space, leads to a loss of the endocochlear potential (31).…”

Section: Generation Of the Endocochlear Potentialmentioning

confidence: 99%

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Functional significance of channels and transporters expressed in the inner ear and kidney

Läng

Vallon²,

Knipper³

et al. 2007

American Journal of Physiology-Cell Physiology

201

180

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A number of ion channels and transporters are expressed in both the inner ear and kidney. In the inner ear, K(+) cycling and endolymphatic K(+), Na(+), Ca(2+), and pH homeostasis are critical for normal organ function. Ion channels and transporters involved in K(+) cycling include K(+) channels, Na(+)-2Cl(-)-K(+) cotransporter, Na(+)/K(+)-ATPase, Cl(-) channels, connexins, and K(+)/Cl(-) cotransporters. Furthermore, endolymphatic Na(+) and Ca(2+) homeostasis depends on Ca(2+)-ATPase, Ca(2+) channels, Na(+) channels, and a purinergic receptor channel. Endolymphatic pH homeostasis involves H(+)-ATPase and Cl(-)/HCO(3)(-) exchangers including pendrin. Defective connexins (GJB2 and GJB6), pendrin (SLC26A4), K(+) channels (KCNJ10, KCNQ1, KCNE1, and KCNMA1), Na(+)-2Cl(-)-K(+) cotransporter (SLC12A2), K(+)/Cl(-) cotransporters (KCC3 and KCC4), Cl(-) channels (BSND and CLCNKA + CLCNKB), and H(+)-ATPase (ATP6V1B1 and ATPV0A4) cause hearing loss. All these channels and transporters are also expressed in the kidney and support renal tubular transport or signaling. The hearing loss may thus be paralleled by various renal phenotypes including a subtle decrease of proximal Na(+)-coupled transport (KCNE1/KCNQ1), impaired K(+) secretion (KCNMA1), limited HCO(3)(-) elimination (SLC26A4), NaCl wasting (BSND and CLCNKB), renal tubular acidosis (ATP6V1B1, ATPV0A4, and KCC4), or impaired urinary concentration (CLCNKA). Thus, defects of channels and transporters expressed in the kidney and inner ear result in simultaneous dysfunctions of these seemingly unrelated organs.

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Section: Functions Of Inner Ear Channels and Transporters In Renal Epmentioning

confidence: 96%

Section: K ϩ Cycling In the Inner Earmentioning

confidence: 98%

Section: Generation Of the Endocochlear Potentialmentioning

confidence: 99%

See 1 more Smart Citation

Functional significance of channels and transporters expressed in the inner ear and kidney

Läng

Vallon²,

Knipper³

et al. 2007

American Journal of Physiology-Cell Physiology

201

180

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“…For intravenous injection, a 3 ml solution containing 30 mg/kg bumetanide was made from its stock solution and the control solution and applied to the right jugular vein in 3 min [24] through a catheter.…”

Section: Perilymphatic and Vascular Application Of The Blockersmentioning

confidence: 99%

NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K+ transport that controls the electrochemical properties in the mammalian cochlea

Yoshida

Nin

Ogata

et al. 2014

Pflugers Arch - Eur J Physiol

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Unidirectional K(+) transport across the lateral cochlear wall contributes to the endocochlear potential (EP) of +80 mV in the endolymph, a property essential for hearing. The wall comprises two epithelial layers, the syncytium and the marginal cells. The basolateral surface of the former and the apical membranes of the latter face the perilymph and the endolymph, respectively. Intrastrial space (IS), an extracellular compartment between the two layers, exhibits low [K(+)] and a potential similar to the EP. This IS potential (ISP) dominates the EP and represents a K(+) diffusion potential elicited by a large K(+) gradient across the syncytial apical surface. The K(+) gradient depends on the unidirectional K(+) transport driven by Na(+),K(+)-ATPases on the basolateral surface of each layer and the concomitant Na(+),K(+),2Cl(-)-cotransporters (NKCCs) in the marginal cell layer. The NKCCs coexpressed with the Na(+),K(+)-ATPases in the syncytial layer also seem to participate in the K(+) transport. To test this hypothesis, we examined the electrochemical properties of the lateral wall with electrodes measuring [K(+)] and potential. Blocking NKCCs by perilymphatic perfusion of bumetanide suppressed the ISP. Unexpectedly and unlike the inhibition of the syncytial Na(+),K(+)-ATPases, the perfusion barely altered the electrochemical properties of the syncytium but markedly augmented [K(+)] of the IS. Consequently, the K(+) gradient decreased and the ISP declined. These observations resembled those when the marginal cells' Na(+),K(+)-ATPases or NKCCs were blocked with vascularly applied inhibitors. It is plausible that NKCCs in the marginal cells are affected by the perilymphatically perfused bumetanide, and these transporters, but not those in the syncytium, mediate the unidirectional K(+) transport.

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“…In Übereinstimmung mit dem vorgestellten Modell führt die Gabe von Ouabain, einem Blocker der Na,K-ATPase, oder von Furosemid, einem Blocker des Na + /Cl − /K + -Cotransporters, zum Zusammenbruch des endokochlearen Potentials [9][10][11][12].…”

Section: Introductionunclassified

Kaliumionensekretion und Entstehung des endokochlearen Potentials in der Stria vascularis

Wangemann

1997

HNO

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Central to inner ear research are questions regarding the homeostasis of the high endolymphatic potassium concentration (approximately 150 mmol/l) and the high endocochlear potential (approximately +80 mV). Disturbances of the endocochlear potential can lead to the immediate loss of hearing which may be irreversible. The molecular mechanism leading to the generation of the endocochlear potential has not yet been discovered in spite of its clinical relevance. It is long known, however, that the stria vascularis is responsible for both the generation of the endocochlear potential as well as the secretion of potassium into endolymph. Recent investigations have clarified the mechanisms leading to the secretion of potassium and have led to the formulation of a now widely accepted model. This model explaining potassium secretion as well as the generation of the endocochlear potential is discussed in the present article.

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Reduction of the Endocochlear Potential by the New “Loop” Diuretic, Bumetanide

Cited by 37 publications

References 24 publications

Functional significance of channels and transporters expressed in the inner ear and kidney

Functional significance of channels and transporters expressed in the inner ear and kidney

NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K+ transport that controls the electrochemical properties in the mammalian cochlea

Kaliumionensekretion und Entstehung des endokochlearen Potentials in der Stria vascularis

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