Putting ion channels to work: mechanoelectrical transduction, adaptation, and amplification by hair cells

Abstract

As in other excitable cells, the ion channels of sensory receptors produce electrical signals that constitute the cellular response to stimulation. In photoreceptors, olfactory neurons, and some gustatory receptors, these channels essentially report the results of antecedent events in a cascade of chemical reactions. The mechanoelectrical transduction channels of hair cells, by contrast, are coupled directly to the stimulus. As a consequence, the mechanical properties of these channels shape our hearing process from the outset of transduction. Channel gating introduces nonlinearities prominent enough to be measured and even heard. Channels provide a feedback signal that controls the transducer's adaptation to large stimuli. Finally, transduction channels participate in an amplificatory process that sensitizes and sharpens hearing.

Figure 1

Mechanical behaviors of a hair bundle. Although a bundle may contain from ≈20 to >300 stereocilia, it is represented here by only two. The sizes of various constituents are distorted for the sake of clarity; in reality, a stereocilium (black) is <1 μm to ≈100 μm in length, a tip link (pink) is ≈150 nm long, a channel (yellow) is <10 nm in diameter, and its gate (orange) moves by ≈4 nm. The actual movements of a hair bundle are far smaller than illustrated: a robust stimulus (60 dB sound-pressure level) deflects the bundle only ±10 nm, half the thickness of the stereociliary outline depicted here, whereas a threshold stimulus moves the bundle less than one-tenth that far. (A) Resting strain. The stereocilia extend initially straight from the apical surface of a hair cell. When a tip link joins contiguous processes, however, it draws the stereociliary tips together and cocks the bundle in the negative direction to its resting position. The tension in the tip link then balances the strain in the actin-filled pivots at the stereociliary bases. (B) Gating compliance. Application to a hair bundle of a positively directed force (green arrow) extends the tip link. When a channel opens (curved orange arrow), the associated tip link shortens, and the tension in the link falls. Relaxation of the tip link acts like an external force in the positive direction, causing the bundle to move still further (red arrow). (C) Adaptation. A positive stimulus force (green arrow) initially deflects the hair bundle, opening a transduction channel. A Ca²⁺ ion (red) that enters through the channel interacts with a molecular motor, probably myosin Iβ, and causes it to slip down the stereocilium's actin cytoskeleton (orange arrow). Slackening of the tip link fosters a slow movement of the bundle in the positive direction (dashed red arrow). The reduced tension in the tip link then permits the channel to reclose. (D) Amplification. When a hair bundle is deflected by the positive phase of a sinusoidal stimulus (upper green arrows), channel opening facilitates bundle movement (upper red arrow). A Ca²⁺ ion (red) that enters through the transduction channel binds to a cytoplasmic site on or associated with the channel, promoting its reclosure. As the channel shuts, the increased tension in the tip link exerts a force that moves the bundle in the negative direction (lower red arrow), enhancing the effect of the negatively directed phase of a stimulation (lower green arrows). When the ion is extruded by a membrane Ca²⁺ pump, or Ca²⁺-ATPase (orange arrow), the hair bundle is primed to repeat the cycle.

Figure 2

Gating of ion channels. (A) Gating of a mechanically sensitive ion channel. The large plot relates hair-bundle displacement (X) to the external force applied to the bundle (F_HB). As a result of gating compliance, channel gating is highly sensitive over a narrow range of forces. The green lines portray the linear relations expected if the channels were to remain closed (top line), open (bottom line), or both in equal numbers (middle line). The curve was obtained by numerically solving a transcendental equation, the inverse of Eq. 5; the parameter values were n = 35, γ = 0.14, κ = 1200 μN⋅m⁻¹, d = 4 nm, z = 0.67 pN, and K_SP = 200 μN⋅m⁻¹. The plot at the left represents the Boltzmann relation between displacement and the channel's open probability (Eq. 3); the displacement axis is identical to that in the principal graph. The graph at the bottom displays the dependence of the channel's open probability on hair-bundle force; the force axis accords with that in the main plot. Note the steepness of this relation, in comparison both to that of a Boltzmann curve and especially to that of the corresponding plot for an electrically activated channel in B. (B) Gating of an electrically sensitive ion channel. The large graph relates membrane potential (V_M) to the charge applied to the membrane (Q_M). As a consequence of gating capacitance, the membrane potential is less responsive to charge over the range of potentials in which channels open and close. The green lines portray the linear relations expected if the channels were to remain closed (left line), open (right line), or both in equal numbers (center line). The curve was obtained by numerically solving a transcendental equation, the inverse of Eq. 12; the numerical values were those provided in the text, with Q₀ = −30 fC. The plot at the left represents the Boltzmann relation between membrane potential and the channel's open probability (Eq. 11); the voltage axis is identical to that in the principal graph. The graph at the bottom displays the dependence of the channel's open probability on the charge applied to the membrane; the charge axis accords with that in the main plot. To facilitate comparison, the four open-probability plots in A and B were scaled such that each extends from p_O = 0.01 to p_O = 0.99.

Figure 3

Mechanically evoked response of a hair bundle from the chicken's cochlea. A damped sinusoidal oscillation of the hair bundle (Upper) ensues from stimulation of a short hair cell situated roughly one-quarter of the distance along the cochlea from its apex. This active mechanical response resembles those recorded earlier from hair cells of the turtle's cochlea and the frog's sacculus, but is severalfold as large and occurs at a higher frequency of ≈235 Hz. An epithelial preparation of the basilar papilla was maintained at room temperature in an oxygenated archosaur saline solution including 1 mM Ca²⁺. The tip of a flexible glass fiber, with a stiffness of 680 μN⋅m⁻¹ and a response time constant of 30 μs, was attached to the bundle's top; stimulation was accomplished by abruptly displacing the fiber's base by 400 nm for 120 ms (Lower). The response represents the output of a dual photodiode onto which an image of the fiber's tip was projected. (×1,000.)