Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

Abstract

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.The high sensitivity of sensory systems requires an efficient use of the energy in stimuli to bias the open probability of ion channels. For a hair cell of the inner ear, mechanical forces directly gate transduction channels atop stereocilia, the rod-like constituents of the mechanosensitive hair bundle 1 . A hair bundle's sensitivity is determined by the relation between the applied force and the number of channels opened: the narrower the force range over which gating occurs, the greater the sensitivity. The coordinated gating of transduction channels is also thought to underlie active hair-bundle motility, a component of the active process that amplifies and tunes the responses of hair cells 2 .Because mechanical stimuli are ordinarily applied at the tall edge of a hair bundle, channel gating depends upon the propagation of mechanical force across the array of stereocilia. Each stereocilium possesses a basal rootlet of actin filaments that tends to hold the process upright; as measured at the hair bundle's tip, the combined stiffness of these stereociliary pivots is about 200 μN·m −1 (ref.3). In addition, the successive stereocilia in each file are joined by tip links that are thought to represent the gating springs attached to transduction channels at one or both ends. For large bundle deflections and in the presence of a physiological concentration of Ca 2+ , the combined stiffness of these gating springs is typically 1000 μN·m −1 (ref. HHMI Author Manuscript HHMI Author Manuscript HHMI Author Manuscriptsprings-the phenomenon of gating compliance-to a value comparable to that of the pivots, or even lower 4,5 .The stereocilia of a hair bundle appear at first glance to be connected in a series-parallel configuration such that a force applied to the tallest stereocilium in each file would first deflect that process alone (Fig. 1a). Movement of the tallest stereocilium would then tighten the tip link and perhaps other filaments connecting it to the second, deflecting that process; the second stereoc...

Horizontal Top Connectors Mediate a Sliding Adhesion to Hair Cell Stereocilia

“…Optical measurements confirmed that the bundle moves as a unit even up to high frequencies [12,14], at least for small deflections (<50 nm). On the other hand, video measurements of chick hair cells [9] suggested that stereocilia do not move uniformly, and some modeling efforts have assumed that only tip links hold stereocilia together [15].…”

“…Thus all channels get essentially the same stimulus. If elements other than tip links hold stereocilia tightly together, then transduction channels are mechanically in parallel [12,14]. With a force stimulus, the parallel arrangement of channels can lead to positive cooperativity.…”

“…The curved cuticular plate would tend to push stereocilia tips together [14]. We measured rootlets from electron micrographs and found that they bend as they insert into the cuticular plate, by an angle of ∼7 • , that might be predicted to push the tips towards the center.…”

Anomalous Brownian motion discloses viscoelasticity in the ear’s mechanoelectrical-transduction apparatus

“…This result indicates that reverse electromechanical transduction is not responsible for subdiffusion. To test whether BAPTA or any of the other drugs caused hairbundle damage, we used a dual-beam laser interferometer directed at the opposite edges of the hair bundle (20) and established that after the pharmacological treatments the stereociliary movements remained coherent, ruling out gross rearrangements of bundle geometry as the cause of the cessation of subdiffusion. Moreover, in line with previous observations (21,22), damaged hair bundles that became incoherent produced a broad spectrum of subdiffusive behaviors regardless of any pharmacological treatments.…”

Damping Properties of the Hair Bundle

“…1C,D; [11]). This unitary movement of the bundle is significantly less dissipative than the displacement pattern with relative motion [10].…”