Limiting dynamics of high-frequency electromechanical transduction of outer hair cells

Abstract

High-frequency resolution is one of the salient features of peripheral sound processing in the mammalian cochlea. The sensitivity originates in the active amplification of the travelling wave on the basilar membrane by the outer hair cells (OHCs), where electrically induced mechanical action of the OHC on a cycle-by-cycle basis is believed to be the crucial component. However, it is still unclear if this electromechanical action is sufficiently fast and can produce enough force to enhance mechanical tuning up to the highest frequencies perceived by mammals. Here we show that isolated OHCs in the microchamber configuration are able to overcome f luid forces with almost constant displacement amplitude and phase up to frequencies well above their placefrequency on the basilar membrane. The high-frequency limit of the electromotility, defined as the frequency at which the amplitude drops by 3 dB from its asymptotic low-frequency value, is inversely dependent on cell length. The frequency limit is at least 79 kHz. For frequencies up to 100 kHz, the electromotile response was specified by an overdamped (Q ‫؍‬ 0.42) second-order resonant system. This finding suggests that the limiting factor for frequencies up to 100 kHz is not the speed of the motor but damping and inertia. The isometric force produced by the OHC was constant at least up to 50 kHz, with amplitudes as high as 53 pN͞mV being observed. We conclude that the electromechanical transduction process of OHCs possesses the necessary high-frequency properties to enable amplification of the travelling wave over the entire hearing range.The discovery of electrically induced length changes of isolated outer hair cells (OHCs) (1), the so-called electromotility, provided the experimental basis for a previously proposed mechanism for the action of OHCs as putative cochlear amplifiers (2): Electrical energy from mechanoelectrical transduction in the stereocilia is converted into mechanical energy by electromechanical transduction in the cell wall. This mechanical energy, converted on a cycle-by-cycle basis, is fed back into the cochlear partition, thereby enhancing mechanoelectrical transduction. One of the most important questions concerns the frequency response of the electromotility and the mechanical force generated by the OHC (3). The frequency range of auditory signals perceived by mammals extends from several Hz to more than 100 kHz for small insect-hunting bats (4). Therefore, any mechanism proposed for amplifying mechanical signals in the cochlea, such as electromotility, must act at all frequencies in this range. Because of the capacitance of the lateral cell membrane, the OHC receptor potential, which drives the electromotility (5-8), is low-pass filtered with corner frequencies between 30 Hz for apical OHCs and 1 kHz for basal OHCs (9,10). This electrical filtering, together with the high-frequency increase of the resistive and inertial fluid forces, is expected to cause severe attenuation of the electromotility at high frequencies in vivo. By holdi...

Organ of Corti Potentials and the Motion of the Basilar Membrane

“…Therefore, an increasing phase lead for the electric potentials would have to be compensated by an equally large phase change of outer hair cell motility to generate the BM tuning curves that we measured. Such frequency-dependent phase change was not found in studies of outer hair cell motility in vitro (Frank et al, 1999). Conceivably, passive mechanical elements within the organ could introduce such a phase lag.…”

“…Length and stiffness changes depend on a specialized motor protein, prestin (Zheng et al, 2000). Electrically evoked hair cell motility is fast, with an upper frequency limit of at least 80 kHz (Frank et al, 1999;Grosh et al, 2004). Most theories of hearing organ function assume that force generated by prestin amplifies the motion of the organ, yielding a large increase of auditory sensitivity (Brownell et al, 1985;Ashmore, 1987;Ruggero and Rich, 1991;Evans and Dallos, 1993;Nuttall and Ren, 1995;Liberman et al, 2002;Fridberger and Boutet de Monvel, 2003).…”

Glycosylation Regulates Prestin Cellular Activity

“…The lateral membrane of the OHC is a highly specialized structure adapted for electromechanical transduction at frequencies approaching 100 kHz (Frank et al 1999;Brownell et al 2001;Brownell 2006;Ashmore 2008). The lateral wall of the adult OHC is low in cholesterol (Santi et al 1994;Nguyen and Brownell 1998;Oghalai et al 1999;Brownell and Oghalai 2000;Rajagopalan et al 2007).…”

Investigating Outer Hair Cell Motility with a Combination of External Alternating Electrical Field Stimulation and High-speed Image Analysis

“…This is a simple and non-invasive technique that circumvents most of the limitations of previous approaches [9][10][11] . Moreover, the LED-based illumination system provides extreme brightness with insignificant thermal effects on the samples and, because of the use of video microscopy, optical resolution is at least 10-fold higher than with conventional light microscopy techniques 12 .…”