Blockage of the transduction channels of hair cells in the bullfrog's sacculus by aminoglycoside antibiotics

Kroese, A.B.A.; Das, Arvind Kumar; Hudspeth, A. J.

doi:10.1016/0378-5955(89)90023-3

Cited by 240 publications

(158 citation statements)

References 56 publications

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“…3). WT ears consistently yielded microphonic responses with peak-to-peak amplitudes of 150-200 V. These signals were eliminated by the extracellular application of gentamicin, a blocker of the mechanically activated current in hair cells (23), thereby validating mechanotransduction as the source of the electrical response (data not shown).…”

Section: Resultsmentioning

confidence: 86%

A nonsense mutation in the gene encoding a zebrafish myosin VI isoform causes defects in hair-cell mechanotransduction

Kappler

Starr²,

Chan³

et al. 2004

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

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In a three-generation screen of chemically mutagenized zebrafish, we identified a group of mutations that affect the development and function of hair cells, the mechanically sensitive cells of the inner ear and lateral-line organ. One mutant line, ru920, was discovered in a behavioral screen for defects in the acoustically evoked escape response. Despite apparently normal numbers of hair cells, mutants lack an inner-ear microphonic potential and exhibit reduced labeling of hair cells by a fluorophore that traverses transduction channels. This hair-cell-specific phenotype suggested a defect in the mechanoelectrical transduction apparatus. Positional cloning revealed that the recessive mutation introduces a premature stop codon in the ORF of myosin6b (myo6b), one of the two zebrafish orthologs of the human gene myosin VI. The ru920 line therefore provides an animal model with which to study the role of class VI myosin proteins in mechanotransduction.

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Section: Resultsmentioning

confidence: 86%

A nonsense mutation in the gene encoding a zebrafish myosin VI isoform causes defects in hair-cell mechanotransduction

Kappler

Starr²,

Chan³

et al. 2004

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

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“…Assuming a diffusion coefficient of 400 m 2 ⅐s Ϫ1 for gentamicin and a value of 0.013 for the ratio of the drug's transference number to its valence (24), we used the diffusion equation to estimate the concentration of gentamicin at the top of the bundle. Even for a 3-nA current from an electrode 5 m above the bundle, the steady-state concentration reached Ϸ16 M, a level sufficient to block most of the transduction channels (24,25).…”

Section: Methodsmentioning

confidence: 99%

Hair-bundle movements elicited by transepithelial electrical stimulation of hair cells in the sacculus of the bullfrog

Bozovic

Hudspeth

2003

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

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Electrically evoked otoacoustic emission is a manifestation of reverse transduction by the inner ear. We present evidence for a single-cell correlate of this phenomenon, hair-bundle movement driven by transepithelial electrical stimulation of the frog's sacculus. Responses could be observed at stimulus frequencies up to 1 kHz, an order of magnitude higher than the organ's natural range of sensitivity to acceleration or sound. Measurements at highstimulus frequencies and pharmacological treatments allow us to distinguish two mechanisms that mediate the electrical responses: myosin-based adaptation and Ca 2؉ -dependent reclosure of transduction channels. These mechanisms also participate in the active process that amplifies and tunes the mechanical responses of this receptor organ. Transient application of the channel blocker gentamicin demonstrated the crucial role of mechanoelectrical transduction channels in the rapid responses to electrical stimulation. A model for electrically driven bundle motion that incorporates the negative stiffness of the hair bundle as well as its two mechanisms of motility captures the essential features of the measured responses.

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“…In this scope, it has been common to use aminoglycoside antibiotics to damage fish inner ear hair cells and then observe the regenerative process (Matsuura et al, 1971;Lombarte et al, 1993). These antibiotics are known to displace calcium ions from their receptors, thereby blocking the cation channels that are located at the apices of hair cell stereocilia (Hudspeth, 1983;Kroese et al, 1989). Among aminoglycoside antibiotics, gentamicin effects are reversible at low concentrations (Wersäll and Flock, 1964).…”

Section: Introductionmentioning

confidence: 99%

Effects of systemic versus local gentamicin on the inner ear in the Atlantic cod, Gadus morhua (L.), relevance for fish hearing investigations

et al. 2008

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a b s t r a c tFish models are increasingly being used for hearing research investigations. Aminoglycoside antibiotics that are used for damaging the inner ear hair cells can have systemic side effects leading to death of study animals. This study aimed to compare two methods: (i) systemic (intravenous) and (ii) local (intrasaccular) gentamicin administration for induction of inner ear hair cell damage in the Atlantic cod, Gadus morhua (L.). Hair cell damage was assessed using scanning electron microscopy; hair cell density, prevalence of immature hair cells and kinocilia length were measured. Gentamicin-treated fish were compared with control and sham fish. Intravenous gentamicin led to dose-dependent mortality caused by nephrotoxicity. The only visible effect after treatment was more immature hair cells and shorter kinocilia, the effect on hair cell density was equivocal. Following intrasaccular gentamicin treatment, fish mortality was negligible, and hair cells were damaged regardless of dose. Here, we observed decreased hair cell density, high prevalence of immature hair cells, and significantly shortened kinocilia. Conclusion: intrasaccular injection is preferable to intravenous injection of gentamicin for the study of ototoxicity in the Atlantic cod.

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Blockage of the transduction channels of hair cells in the bullfrog's sacculus by aminoglycoside antibiotics

Cited by 240 publications

References 56 publications

A nonsense mutation in the gene encoding a zebrafish myosin VI isoform causes defects in hair-cell mechanotransduction

A nonsense mutation in the gene encoding a zebrafish myosin VI isoform causes defects in hair-cell mechanotransduction

Hair-bundle movements elicited by transepithelial electrical stimulation of hair cells in the sacculus of the bullfrog

Effects of systemic versus local gentamicin on the inner ear in the Atlantic cod, Gadus morhua (L.), relevance for fish hearing investigations

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