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

1992 ◽  
Vol 68 (3) ◽  
pp. 927-932 ◽  
Author(s):  
W. Denk ◽  
R. M. Keolian ◽  
W. W. Webb
Keyword(s):  
Hair Cells ◽  
Mechanical Response ◽  
Low Frequency ◽  
Initial Deflection ◽  
Published Data ◽  
Adaptation Mechanism ◽  
Mechanical Adaptation ◽  
Mechanoelectrical Transduction ◽  
Displacement Sensitivity ◽  
Hair Bundles

1. Deflections of the mechanosensory hair bundles on frog saccular hair cells were measured interferometrically, with submillisecond temporal and submicrometer spatial resolution, and with subnanometer displacement sensitivity. 2. The direction of the initial bundle deflection (toward the taller stereocilia) in response to a sudden application of aminoglycoside antibiotics shows that the mechanosensory channels are blocked in their mechanically open state. 3. The magnitude of the initial deflection is consistent with published data on the gating swing as derived from the gating compliance. 4. A delayed relaxation and frequently a reversal of the initial deflection were observed and are attributed to the previously reported mechanical adaptation mechanism, which is at least partially controlled by the influx of Ca2+ through the transduction channels. 5. Increases of low-frequency spontaneous motion were found at intermediate blocker concentrations. They can be well accounted for by the fluctuating force exerted on the bundle by the random binding and unbinding of blocker molecules. 6. The mechanical response of the hair bundle to aminoglycosides may be related to their acute and specific ototoxicity.

scholarly journals An unusually powerful mode of low-frequency sound interference due to defective hair bundles of the auditory outer hair cells

2014 ◽  
Vol 111 (25) ◽  
pp. 9307-9312 ◽  
Author(s):  
K. Kamiya ◽  
V. Michel ◽  
F. Giraudet ◽  
B. Riederer ◽  
I. Foucher ◽  
...  
Keyword(s):  
Hair Cells ◽  
Low Frequency ◽  
Outer Hair Cells ◽  
Frequency Sound ◽  
Hair Bundles

scholarly journals Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

2016 ◽  
Vol 212 (2) ◽  
pp. 231-244 ◽  
Author(s):  
Andrea Lelli ◽  
Vincent Michel ◽  
Jacques Boutet de Monvel ◽  
Matteo Cortese ◽  
Montserrat Bosch-Grau ◽  
...  
Keyword(s):  
Hair Cells ◽  
Late Onset ◽  
Critical Role ◽  
Normal Hearing ◽  
Hair Bundle ◽  
Class Iii ◽  
Auditory Hair Cells ◽  
Mechanoelectrical Transduction ◽  
Hair Bundles ◽  
Myosin Iiia

The precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a−/−Myo3b−/− mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b−/− mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a−/−Myo3b−/− cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a−/−Myo3b−/− stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping.

scholarly journals Rheology of rounded mammalian cells over continuous high-frequencies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gotthold Fläschner ◽  
Cosmin I. Roman ◽  
Nico Strohmeyer ◽  
David Martinez-Martin ◽  
Daniel J. Müller
Keyword(s):  
High Frequency ◽  
Mammalian Cells ◽  
Mechanical Response ◽  
Cell Mass ◽  
Low Frequency ◽  
Mass Measurements ◽  
High Frequencies ◽  
Polymer Relaxation ◽  
Continuous Frequency ◽  
Rheological Experiments

AbstractUnderstanding the viscoelastic properties of living cells and their relation to cell state and morphology remains challenging. Low-frequency mechanical perturbations have contributed considerably to the understanding, yet higher frequencies promise to elucidate the link between cellular and molecular properties, such as polymer relaxation and monomer reaction kinetics. Here, we introduce an assay, that uses an actuated microcantilever to confine a single, rounded cell on a second microcantilever, which measures the cell mechanical response across a continuous frequency range ≈ 1–40 kHz. Cell mass measurements and optical microscopy are co-implemented. The fast, high-frequency measurements are applied to rheologically monitor cellular stiffening. We find that the rheology of rounded HeLa cells obeys a cytoskeleton-dependent power-law, similar to spread cells. Cell size and viscoelasticity are uncorrelated, which contrasts an assumption based on the Laplace law. Together with the presented theory of mechanical de-embedding, our assay is generally applicable to other rheological experiments.

scholarly journals The Sampling Distribution of Disease-Associated Alleles

Genetics ◽  
1997 ◽  
Vol 147 (4) ◽  
pp. 1855-1861 ◽  
Author(s):  
Montgomery Slatkin ◽  
Bruce Rannala
Keyword(s):  
Low Frequency ◽  
Null Model ◽  
Sampling Distribution ◽  
Death Process ◽  
Published Data ◽  
Data Sets ◽  
Likelihood Functions ◽  
Alternative Hypotheses ◽  
Size Standard ◽  
Birth Death

Abstract A theory is developed that provides the sampling distribution of low frequency alleles at a single locus under the assumption that each allele is the result of a unique mutation. The numbers of copies of each allele is assumed to follow a linear birth-death process with sampling. If the population is of constant size, standard results from theory of birth-death processes show that the distribution of numbers of copies of each allele is logarithmic and that the joint distribution of numbers of copies of k alleles found in a sample of size n follows the Ewens sampling distribution. If the population from which the sample was obtained was increasing in size, if there are different selective classes of alleles, or if there are differences in penetrance among alleles, the Ewens distribution no longer applies. Likelihood functions for a given set of observations are obtained under different alternative hypotheses. These results are applied to published data from the BRCA1 locus (associated with early onset breast cancer) and the factor VIII locus (associated with hemophilia A) in humans. In both cases, the sampling distribution of alleles allows rejection of the null hypothesis, but relatively small deviations from the null model can account for the data. In particular, roughly the same population growth rate appears consistent with both data sets.

scholarly journals Hearing at threshold intensities: by slow mechanical traveling waves or by fast cochlear fluid pressure waves

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haim Sohmer
Keyword(s):  
Soft Tissue ◽  
Hair Cells ◽  
Traveling Wave ◽  
Basilar Membrane ◽  
Fluid Pressure ◽  
Low Frequency ◽  
Frequency Discrimination ◽  
Outer Hair Cells ◽  
Common Mechanism ◽  
Frequency Stimulation

The three modes of auditory stimulation (air, bone and soft tissue conduction) at threshold intensities are thought to share a common excitation mechanism: the stimuli induce passive displacements of the basilar membrane propagating from the base to the apex (slow mechanical traveling wave), which activate the outer hair cells, producing active displacements, which sum with the passive displacements. However, theoretical analyses and modeling of cochlear mechanics provide indications that the slow mechanical basilar membrane traveling wave may not be able to excite the cochlea at threshold intensities with the frequency discrimination observed. These analyses are complemented by several independent lines of research results supporting the notion that cochlear excitation at threshold may not involve a passive traveling wave, and the fast cochlear fluid pressures may directly activate the outer hair cells: opening of the sealed inner ear in patients undergoing cochlear implantation is not accompanied by threshold elevations to low frequency stimulation which would be expected to result from opening the cochlea, reducing cochlear impedance, altering hydrodynamics. The magnitude of the passive displacements at threshold is negligible. Isolated outer hair cells in fluid display tuned mechanical motility to fluid pressures which likely act on stretch sensitive ion channels in the walls of the cells. Vibrations delivered to soft tissue body sites elicit hearing. Thus, based on theoretical and experimental evidence, the common mechanism eliciting hearing during threshold stimulation by air, bone and soft tissue conduction may involve the fast-cochlear fluid pressures which directly activate the outer hair cells.

Tinnitus: some thoughts about its origin

1984 ◽  
Vol 98 (S9) ◽  
pp. 31-37 ◽  
Author(s):  
J. J. Eggermont
Keyword(s):  
Hair Cells ◽  
High Frequency ◽  
Basilar Membrane ◽  
Stimulus Frequency ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Ear Ossicles ◽  
Stimulus Transduction ◽  
Low Levels ◽  
Inner Ear Fluids

An auditory sensation follows generally as the result of the sequence stimulus, transduction, coding, transformation and sensation. This is then optionally followed by perception and a reaction. The stimulus is usually airborne sound causing movements of the tympanic membrane, the middle ear ossicles, the inner ear fluids and the basilar membrane. The movements of the basilar membrane are dependent on stimulus frequency: high frequency tones excite only the basal part of the cochlea, regardless of the stimulus intensity; low frequency tones at low levels only excite the so-called place specific region at the apical end but at high levels (above 60–70 dB SPL) cause appreciable movement of the entire basilar membrane. Basilar membrane tuning is as sharp as that of inner hair cells or auditory nerve fibers (Sellick et al., 1982) at least in the basal turn of animals that have a cochlea in physiologically impeccable condition.

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