Mechanical response of frog saccular hair bundles to the aminoglycoside block of mechanoelectrical transduction

Denk, Winfried; Keolian, Robert M.; Webb, W. W.

doi:10.1152/jn.1992.68.3.927

Cited by 43 publications

(41 citation statements)

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“…Aminoglycosides are used routinely to block the mechanoelectrical transduction channel (Denk et al 1992). Thus, the presence of GTTR and immunolabeled gentamicin at the location of the hair bundle of mature and immature hair cells is unsurprising, corroborating previous reports (Tachibana et al 1985(Tachibana et al , 1986Richardson et al 1989).…”

Section: Distribution Of Gttr Fluorescencesupporting

confidence: 80%

Uptake of Gentamicin by Bullfrog Saccular Hair Cells in vitro

Steyger

Peters

Rehling

et al. 2003

JARO - Journal of the Association for Research in Otolaryngolog

104

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Vertebrate sensory hair cells in the inner ear are pharmacologically sensitive to aminoglycoside antibiotics. Although the ototoxicity of aminoglycosides is well known, the route of drug uptake by hair cells and mechanisms of cytotoxicity remain poorly understood. Previously published studies have documented the intracellular distribution of gentamicin using immunocytochemical, electron microscopic, and autoradiographic methods. In this article, we compare the subcellular distribution of fluorescently conjugated gentamicin (gentamicin-Texas Red, GTTR) with immunolabeled gentamicin using confocal or electron microscopy. Gentamicin (detected by postfixation immunocytochemistry) and GTTR were rapidly taken up by hair cells throughout the bullfrog saccular explant in vitro and preferentially in peripheral hair cells. Immunolabeled gentamicin and GTTR were observed at the apical membranes of hair cells, particularly in their hair bundles. GTTR was also identified within a variety of subcellular compartments within hair cells, including lysosomes, mitochondria, Golgi bodies, endoplasmic reticulum, and nuclei, and in similar structures by immunoelectron microscopy. The distributions of GTTR and immunolabeled gentamicin are largely identical and corroborate a variety of published immunocytochemical and autoradiography studies. Thus, GTTR is a valid fluorescent probe with which to investigate the pharmacokinetics and mechanisms of gentamicin accumulation.

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Section: Distribution Of Gttr Fluorescencesupporting

confidence: 80%

Uptake of Gentamicin by Bullfrog Saccular Hair Cells in vitro

Steyger

Peters

Rehling

et al. 2003

JARO - Journal of the Association for Research in Otolaryngolog

104

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“…This aminoglycoside antibiotic, which rapidly and reversibly blocks transduction channels in the open state (28,29), arrests spontaneous hair-bundle oscillation (P. Martin, D.B., Y. Choe, and A.J.H., unpublished data). After a short delay consistent with the drug's diffusion from an iontophoretic pipette, gentamicin largely suppressed electrically evoked bundle movement (Fig.…”

Section: Resultsmentioning

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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“…3). Nonlinearity of the force-displacement relation could be abolished by aminoglycosides, known open channel blockers (Kroese, Das & Hudspeth, 1989;Denk, Keolian & Webb, 1992;Ricci, 2002;Marcotti, van Netten & Kros, 2005). The prediction is that, when present in the (open) channel pore, these molecules effectively prevent a channel from making a conformational swing to the closed position.…”

Section: Forces Related To Gatingmentioning

confidence: 99%

Mechano-electrical Transduction: New Insights into Old Ideas

et al. 2006

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The gating-spring theory of hair cell mechanotransduction channel activation was first postulated over twenty years ago. The basic tenets of this hypothesis have been reaffirmed in hair cells from both auditory and vestibular systems and across species. In fact, the basic findings have been reproduced in every hair cell type tested. A great deal of information regarding the structural, mechanical, molecular and biophysical properties of the sensory hair bundle and the mechanotransducer channel has accumulated over the past twenty years. The goal of this review is to investigate new data, using the gating spring hypothesis as the framework for discussion. Mechanisms of channel gating are presented in reference to the need for a molecular gating spring or for tethering to the intra-or extracellular compartments. Dynamics of the sensory hair bundle and the presence of motor proteins are discussed in reference to passive contributions of the hair bundle to gating compliance. And finally, the molecular identity of the channel is discussed in reference to known intrinsic properties of the native transducer channel.

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Mechanical response of frog saccular hair bundles to the aminoglycoside block of mechanoelectrical transduction

Cited by 43 publications

References 0 publications

Uptake of Gentamicin by Bullfrog Saccular Hair Cells in vitro

Uptake of Gentamicin by Bullfrog Saccular Hair Cells in vitro

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

Mechano-electrical Transduction: New Insights into Old Ideas

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