Progress in cochlear physiology after Békésy

Abstract

In the fifty years since Békésy was awarded the Nobel Prize, cochlear physiology has blossomed. Many topics that are now current are things Békésy could not have imagined. In this review we start by describing progress in understanding the origin of cochlear gross potentials, particularly the cochlear microphonic, an area in which Békésy had extensive experience. We then review progress in areas of cochlear physiology that were mostly unknown to Békésy, including: (1) stereocilia mechano-electrical transduction, force production, and response amplification, (2) outer hair cell (OHC) somatic motility and its molecular basis in prestin, (3) cochlear amplification and related micromechanics, including the evidence that prestin is the main motor for cochlear amplification, (4) the influence of the tectorial membrane, (5) cochlear micromechanics and the mechanical drives to inner hair cell stereocilia, (6) otoacoustic emissions, and (7) olivocochlear efferents and their influence on cochlear physiology. We then return to a subject that Békésy knew well: cochlear fluids and standing currents, as well as our present understanding of energy dependence on the lateral wall of the cochlea. Finally, we touch on cochlear pathologies including noise damage and aging, with an emphasis on where the field might go in the future.

Fig. 1

A schematic of OHC mechano-electric transduction (MET) and prestin conformational change. A: Tip links connect the MET apparatus on short stereocilia (expanded in B) with the next taller stereocilia. Circled is a prestin-containing patch of lateral membrane (expanded in C). Deflection toward the tallest stereocilia pulls on the tip links and increases the probability that the channels will open. Deflection toward the smallest stereocilia does the opposite. B: Cartoon of the MET channel protein in the open (green) and closed (red) state. When the channel is open, potassium (K⁺) and calcium (Ca²⁺) ions flow into the OHC. Calcium ions bind to a nearby site, which reduces the open probability, perhaps by relaxing a spring-like element. The binding site is shown here in a second protein molecule, even though the actual configuration remains unknown. The receptor current carried by potassium ions depolarizes the OHC. C-top: OHC depolarization (DEPOL) causes prestin molecules to become narrower resulting in OHC somatic contraction. C-bottom: OHC hyperpolarization (HYPERP) causes prestin molecules to become wider resulting in OHC somatic elongation.

Fig. 2

Steps in the cochlear amplification of basilar membrane (BM) motion for BM movement towards scala vestibuli. 1. The pressure difference across the cochlear partition causes the BM to move up. 2. The upward BM movement causes rotation of the organ of Corti about the foot of the inner pillar (IP), movement of the reticular lamina (RL) toward the modiolus (left) and shear of the RL relative to the tectorial membrane (TM) that deflects stereocilia in the excitatory direction (green arrow). 3. This deflection of outer hair cell (OHC) stereocilia opens mechano-electric-transduction channels, which increases the receptor current driven into the OHC (blue arrow) by the potential difference between the +100 mV endocochlear potential and the ~-40 mV OHC resting potential. The receptor current flowing through the impedance of the hair cell’s basolateral surface depolarizes the cell. In contrast to OHCs that are displacement detectors, inner hair cells (IHC) are sensitive to velocity, at least at low frequencies, because their hair bundles are not firmly imbedded in the overlying TM. 4. OHC depolarization causes conformational changes in individual prestin molecules that sum to induce a reduction in OHC length. The OHC contraction pulls the BM upward toward the RL, which amplifies BM motion when the pull on the BM is in the correct phase. As noted in the text, it also produces downward RL motion in the OHC region and upward motion in the IHC region due to RL pivoting. The downward RL motion in the OHC region is opposite from the RL motion produced in steps 1–2, which effectively applies negative feedback on the RL motion that is the drive to the OHC (see Lu et al., 2006). The RL pivoting and resulting fluid flow in the subtectorial space may provide an additional mechanism by which OHC motility may enhance the mechanical drive to IHC stereocilia (see text section 7).