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An intrinsic frequency limit to the cochlear amplifier

Nature volume 389, pages 63–66 (1997)Cite this article

Hearing in mammals depends on a feedback process within the inner ear termed the ‘cochlear amplifier’1. The essential components of this amplifier are sensorimotor cells, the outer hair cells, which transduce motion of the basilar membrane induced by sound and generate forces to cancel the viscous damping of the cochlear partition2,3. Outer hair cells alter the passive mechanics of the cochlea, enhancing both the sensitivity and the frequency selectivity of the auditory system. The molecular basis of the mechanism is thought to be a voltage-sensitive ‘motor’ protein, as yet unidentified, embedded in the basolateral membrane of the outer hair cell4. The cochlear amplifier operates up to at least 22 kHz (ref. 5), but by measuring both the charge and mechanical movements associated with the motor6,7 in isolated membrane patches under voltage clamp, we show here that the limiting frequency at which the motor operates lies near 25 kHz. This value therefore sets an upper limit to the range of hearing in mammalian cochleas using this mechanism. The fast charge movement, arising from charge displacement within the presumed motor molecule, further suggests that the protein is more likely to be related to a transporter than to a modified ion channel.

which is a Boltzmann distribution where Qmax represents the maximum charge transferred, V0 is the potential at which the charge is distributed equally6,7,11, β= zeδkBT and is a constant given by the number, z, of elementary charges, e, displaced across a fraction, δ, of the membrane dielectric, kB is Boltzmann's constant and T is the absolute temperature. This model describes the movement of positive charge from the inside to the outside of the membrane when the membrane potential is stepped from a negative to a positive potential. Wide-band recordings (Fig. 1a, b) indicate that the transient current relaxation could be fitted to a single exponential with a time constant of between 7 and 50 µs. The values depend upon the final potential and so different time constants were obtained for ‘on’ and ‘off’ voltage steps within the same pulse, showing that the responses were not limited by recording bandwidth. The mean time constant averaged for steps to −20 mV was 13.6 ± 6.4 µs (mean ± s.d., n = 10). The shortest time constants measured in 10 patches were 9.9 ± 1.4 µs for ‘on’ steps to depolarized potentials and 10.5 ± 3.0 µs for ‘off’ steps to hyperpolarized potentials. In 50% of patches the best fit to the transient current was obtained using a combination of two exponentials. The second exponential had a significantly slower time course (range 23 µs to 2.3 ms), which we ascribe to residual contamination by ionic currents. The time constants were temperature dependent (Fig. 1c) with Q10 = 1.34 in the range 10–26 °C. Bath application of 10 mM sodium salicylate reduced the charge movement to 28.5 ± 14.3% of control (n = 3; Fig. 1e). Salicylate also reduces transient currents and motility in whole-cell recording12 and provides further evidence that the transient currents in patches arise from the motor protein.

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Figure 1: Rapid charge movement associated with the OHC motor in isolated membrane patches.
Figure 2: Movement of an isolated OHC patch.
Figure 3: Voltage-dependent capacitance in isolated membrane patches.

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Acknowledgements

This work was supported by the Hearing Research Trust, the Colt Foundation, the Royal Society, and the Wellcome Trust.

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Authors and Affiliations

  1. Department of Physiology, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK

    Jonathan E. Gale & Jonathan F. Ashmore

  2. Department of Physiology, University College London, Gower Street, London, WC1E 6BT, UK

    Jonathan E. Gale & Jonathan F. Ashmore

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Gale, J., Ashmore, J. An intrinsic frequency limit to the cochlear amplifier. Nature 389, 63–66 (1997). https://doi.org/10.1038/37968

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