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    Force Generation by Mammalian Hair Bundles Supports A Role in Cochlear Amplification

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    The document summarizes research on force generation by mammalian hair bundles and its role in cochlear amplification. Experiments measured the motion of hair bundles in response to mechanical stimulation. At first, bundle motion depended linearly on force, but gradually became nonlinear over time, indicating the bundle generated its own opposing force. This force was found to be mediated by calcium ions and adaptation of mechanoelectrical transduction channels. The findings support a role for outer hair cells and hair bundles in actively amplifying sounds in the cochlea.

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    Force Generation by Mammalian Hair Bundles Supports A Role in Cochlear Amplification

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    107bt005
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    The document summarizes research on force generation by mammalian hair bundles and its role in cochlear amplification. Experiments measured the motion of hair bundles in response to mechanical stimulation. At first, bundle motion depended linearly on force, but gradually became nonlinear over time, indicating the bundle generated its own opposing force. This force was found to be mediated by calcium ions and adaptation of mechanoelectrical transduction channels. The findings support a role for outer hair cells and hair bundles in actively amplifying sounds in the cochlea.

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    the function of cochlea.

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    Presentation Biswa Yo1014

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    The document summarizes research on force generation by mammalian hair bundles and its role in cochlear amplification. Experiments measured the motion of hair bundles in response to mechanical stimulation. At first, bundle motion depended linearly on force, but gradually became nonlinear over time, indicating the bundle generated its own opposing force. This force was found to be mediated by calcium ions and adaptation of mechanoelectrical transduction channels. The findings support a role for outer hair cells and hair bundles in actively amplifying sounds in the cochlea.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    40 views24 pages

    Force Generation by Mammalian Hair Bundles Supports A Role in Cochlear Amplification

    Uploaded by

    107bt005
    The document summarizes research on force generation by mammalian hair bundles and its role in cochlear amplification. Experiments measured the motion of hair bundles in response to mechanical stimulation. At first, bundle motion depended linearly on force, but gradually became nonlinear over time, indicating the bundle generated its own opposing force. This force was found to be mediated by calcium ions and adaptation of mechanoelectrical transduction channels. The findings support a role for outer hair cells and hair bundles in actively amplifying sounds in the cochlea.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPTX, PDF, TXT or read online from Scribd
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    of 24

    Force generation by mammalian hair bundles supports a role in cochlear amplification

    H. J. KENNEDY1,2, A. C. CRAWFORD3 & R. FETTIPLACE1 1DEPARTMENT OF PHYSIOLOGY, UNIVERSITY OF W ISCONSIN MEDICAL SCHOO L, MADISON, WISCONSIN 53706, USA 2DEPARTMENT OF PHYSIOLOGY, UNIVERSITY OF BRISTOL, BRISTOL BS8 1T D, UK 3DEPARTMENT OF PHYSIOLOGY, CAMBRIDGE UNIVERSITY, CAMBRIDGE CB2 3 EG, UK

    PRESENTED BY X I YA O L O N G & B I S WA J I T M A H A R AT H I
    CELLULAR BIOMECHANICS UNIVERSITY OF ILLINOIS, CHICAGO

    outline
    -Structure and function of cochlear -Two motor in cochlear participating in amplification -Experimental setups and procedure -Experimental results and discussion

    -Future scope

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    Vibrations of the eardrum are relayed via middle ear Initiate pressure waves in the cochlear fluids Cause the motion the basilar membrane

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    P in the two scalae of the cochlea result in a traveling wave on the basilar membrane

    Their movement is stimulated by the shear force of the membrane caused by the pivot point.

    The outer hair cells, work as microscopic energy pumping motors

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    Somatic motor

    The depolarization led cl- dissociate The prestin changes conformation Shortening the hair cell body

    Downward motion of the reticular lamina

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    Hair bundle motor


    A + deflection opens MET channels Increases stereociliary ca2+ Re-closes the channels and causes the bundle to spring back, recoil. Adaptation: Channel opening: increases hair bundle compliance Ca2+-evoked re-closure of the channel decreases compliance, causing the bundle to move back towards its original resting position.

    Not limited by the membrane time constant, only by the kinetics of the channel activation and adaptation.

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    http://www.youtube.com/watch?v=Xo9bwQuY rRo

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    Method
    To the hair bundles, a glass fiber was attached. The glass fiber was attached to a piezo device that measures the displacement using photodiode.

    For the experiment neonatal rat outer hair cell were used. In some cases mature rat hair cells and cells from turtle were used.

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    Calibration

    Calibration of the system, the linear relationship implies the correct measurement of displacement

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    MET currents Steady state around 8s

    The bundle motion reaches the steady state slightly later than piezo motion This could be explained by displacement latency

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    10

    MET channels increase their (po) with + hair bundle displacement (x).

    Measurements at successive times (t ) after peak current : T=0,bundle behaves like a simple spring in which x is proportional to F T=1~8 the relationship becomes more and more nonlinear and this could be because that the hair bundle would generate its own force

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    11

    FB=XKS-Ap0(X)+F0
    Where KS = passive linear stiffness Po = probability of opening of the MET channels A and F0 are constants and are determined experimentally.
    The ve sign is due to the force, generated in the direction of displacement which leads to the decrease stiffness. ________________ ________________

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    12

    -The nonlinearity is time dependent and progress with adaptation.

    -with a applied force, the current reaches it peak instantaneously, due to adaptation /internal mechanism, gradually decreases.

    -the additional motion of the bundle signifies there is some additional force generated y the bundle.

    Force generation by OHC bundles

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    13

    Boltzmann relation:

    = (1 +

    1
    0

    where I=instanteneous current X=displacement I max = 0.67 nA, Xo = 284 nm and X e = 132 nm.

    Force generation by OHC bundles

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    14

    Why this nonlinearity?

    Due to the force generation in the hair bundles.

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    15

    What causes this nonlinearity?

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    16

    -Analysis says, the force generation in the bundles is a result of events at the MET channel level.

    -MET channel has a dependency on the various factors present in the extracellular environment.

    -Ca++ ion is known for reducing as well slowing down the adaptation.

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    17

    Effect of low Ca++ concentration: - shifted the P0(X) relationship 200nm in ve direction(reduces the negative value). - A was reduced by 21%. Passive stiffness Ks was twice of its value.

    FB=XKS-Ap0(X)+F0
    - The t=0 is the measurement at the peak current, and hence shows the higher values in the force. - The subsequent time point measurements were taken at different displacements. - The values are approximated and correspond to maximum compliance.

    Effect of Ca+2 on OHC mechanism

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    18

    - bundle force develops with the same time course as fast adaptation.

    - Stiffness increased from 1.9 0.6mNm-1 in 1.5mM to Ca+2 to 5.5 1.0mNm-1 in 0.02mM Ca+2

    Effect of Ca+2 on OHC mechanism

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    19

    1.5mM Ca++

    Effect of Ca+2 on OHC mechanism

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    20

    Tiny hair bundles Fast kinetics

    Large force

    How ???

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    21

    -presence of myosin in the hair bundle. Myosin is known for affecting MET channels. Myosin action is not that fast to provide sufficient explanation.

    -MET Channel which might be under going conformational changes MET channels generate force instantaneously. MET Channel adaptation. Different in polarity.

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    22

    Reference

    1. Nam JH, Fettiplace R. Force transmission in the organ of Corti micromachine. Biophys J. 2010;98(12):2813-21. 2. Kennedy, H. J., Evans, M. G., Crawford, A. C. & Fettiplace, R. Fast adaptation of mechanoelectrical transducer channels in mammalian cochlear hair cells. Nature Neurosci. 6, 832836 (2003). 3. Kennedy HJ, Evans MG, Crawford AC, Fettiplace R. Depolarization of cochlear outer hair cells evokes active hair bundle motion by two mechanisms. J Neurosci. 2006;26(10):2757-66.

    4. Kennedy HJ, Crawford AC, Fettiplace R. Force generation by mammalian hair bundles supports a role in cochlear amplification. Nature. 2005;433(7028):880-3.

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

    23

    CELLULAR BIOMECHANICS

    UNIVERSITY OF ILLINOIS, CHICAGO

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