Peter Dallos

Prestin is the motor protein of cochlear outer hair cells.

The outer and inner hair cells of the mammalian cochlea perform different functions. In response to changes in membrane potential, the cylindrical outer hair cell rapidly alters its length and stiffness. These mechanical changes, driven by putative molecular motors, are assumed to produce amplification of vibrations in the cochlea that are transduced by inner hair cells. Here we have identified an abundant complementary DNA from a gene, designated Prestin, which is specifically expressed in outer hair cells. Regions of the encoded protein show moderate sequence similarity to pendrin and related sulphate/anion transport proteins. Voltage-induced shape changes can be elicited in cultured human kidney cells that express prestin. The mechanical response of outer hair cells to voltage change is accompanied by a ‘gating current’, which is manifested as nonlinear capacitance. We also demonstrate this nonlinear capacitance in transfected kidney cells. We conclude that prestin is the motor protein of the cochlear outer hair cell.

Prestin-Based Outer Hair Cell Motility Is Necessary for Mammalian Cochlear Amplification

It is a central tenet of cochlear neurobiology that mammalian ears rely on a local, mechanical amplification process for their high sensitivity and sharp frequency selectivity. While it is generally agreed that outer hair cells provide the amplification, two mechanisms have been proposed: stereociliary motility and somatic motility. The latter is driven by the motor protein prestin. Electrophysiological phenotyping of a prestin knockout mouse intimated that somatic motility is the amplifier. However, outer hair cells of knockout mice have significantly altered mechanical properties, making this mouse model unsatisfactory. Here, we study a mouse model without alteration to outer hair cell and organ of Corti mechanics or to mechanoelectric transduction, but with diminished prestin function. These animals have knockout-like behavior, demonstrating that prestin-based electromotility is required for cochlear amplification.

Prestin, a new type of motor protein

Prestin, a transmembrane protein found in the outer hair cells of the cochlea, represents a new type of molecular motor, which is likely to be of great interest to molecular cell biologists. In contrast to enzymatic-activity-based motors, prestin is a direct voltage-to-force converter, which uses cytoplasmic anions as extrinsic voltage sensors and can operate at microsecond rates. As prestin mediates changes in outer hair cell length in response to membrane potential variations, it might be responsible for sound amplification in the mammalian hearing organ.

Cochlear Inner and Outer Hair Cells: Functional Differences

The cochlear microphonic response was measured with differential electrodes from the first and third cochlear turns of normal guinea pigs and those treated with the ototoxic drug kanamycin. Histological controls showed that the outer hair cells in treated animals were missing over the basal half of the damaged cochleas, while the inner hair cells were intact. Measurements are consistent with the hypothesis that the potentials produced by inner hair cells are proportional to the velocity of the basilar membrane, whereas potentials generated by outer hair cells (which dominate the response of normal cochleas) are proportional displacement of the basilar membrane.

Compound action potential (AP) tuning curves

With a tone‐on‐tone masking procedure the compound action potential (AP), elicited by brief tone bursts of set frequency and intensity, was decreased by a constant fraction. The frequency–intensity pairs formed by the masker that yield this decrease generate the AP tuning curve. It is demonstrated that such tuning curves are very similar to both psychophysical tuning curves and single VIIIth‐nerve‐fiber tuning curves. Changes in the properties of these curves are described as functions of stimulus frequency and level, mode of masking (simultaneous and forward), and parameters of the masker.Subject Classification: [43]65.40, [43]65.42, [43]65.58.

Production of cochlear potentials by inner and outer hair cells

Cochlear microphonic and summating potential recordings were obtained from preparations where only either inner hair cells (first‐turn recording) or outer hair cells (fourth‐turn recording) could have contributed to the potentials. A comparison suggests that outer hair cells do produce the preponderance of receptor potentials.Subject Classification: [43]65.40, [43]65.42.

Neural coding in the chick cochlear nucleus

SummaryPhysiological recordings were made from single units in the two divisions of the chick cochlear nucleus — nucleus angularis (NA) and nucleus magnocellularis (NM). Sound evoked responses were obtained in an effort to quantify functional differences between the two nuclei. In particular, it was of interest to determine if nucleus angularis and magnocellularis code for separate features of sound stimuli, such as temporal and intensity information. The principal findings are:1.Spontaneous activity patterns in the two nuclei are very different. Neurons in nucleus angularis tend to have low spontaneous discharge rates while magnocellular units have high levels of spontaneous firing.2.Frequency tuning curves recorded in both nuclei are similar in form, although the best thresholds of NA units are about 10 dB more sensitive than their NM counterparts across the entire frequency range. A wide spread of neural thresholds is evident in both NA and NM.3.Large driven increases in discharge rate are seen in both NA and NM. Rate intensity functions from NM units are all monotonic, while a substantial percentage (22%) of NA units respond to increased sound level in a nonmonotonic fashion.4.Most NA units with characteristic frequencies (CF) above 1000 Hz respond to sound stimuli at CF as ‘choppers’, while units with CFs below 1000 Hz are ‘primary-like’. Several ‘onset’ units are also seen in NA. In contrast, all NM units show ‘primary-like’ response.5.Units in both nuclei with CFs below 1000 Hz show strong neural phase-locking to stimuli at their CF. Above 1000 Hz, few NA units are phase-locked, while phase-locking in NM extends to 2000 Hz.6.These results are discussed with reference to the hypothesis that NM initiates a neural pathway which codes temporal information while NA is involved primarily with intensity coding, similar in principle to the segregation of function seen in the cochlear nucleus of the barn owl (Sullivan and Konishi 1984).

Neurobiology of cochlear inner and outer hair cells: intracellular recordings

Recordings were made in the low-frequency region (third and fourth turns) of the guinea pig cochlea from both inner (IHC) and outer (OHC) hair cells. Certain electrical characteristics of these cells that have been described before (P. Dallos (1985) J. Neurosci. 5, 1591-1608) are reviewed. These are resting membrane potentials, response magnitude and saturation, and response phase. A comparison of sensitivity and best frequency is provided for IHCs and OHCs that are located in the same cochlear region. New data are presented for the level-dependence of response phase and for the properties of response asymmetry and the resulting dc component. The effects of intracellular polarizing current upon ac response magnitude are shown for both cell types.

Positive endocochlear potential: mechanism of production by marginal cells of stria vascularis

The positive endocochlear potential (EP+) and high K+ concentration of the endolymph in the scala media of the mammalian cochlea are unusual. They have long been assumed to be due to a putative K-pump in the luminal membrane of the marginal cells of the stria vascularis, which were believed to have a negative internal potential. We show that the cell potential is more positive than the EP+, and that the ion pump is conventional Na,K-ATPase, probably in the basolateral membrane. The latter was determined from experiments in which the ionic environment of the strial cells was controlled by perfusion of the perilymphatic space of the cochlea, in the absence of vascular circulation. While the usual EP+ was maintained by normal perfusate, replacement of Na+ by choline resulted in a negative EP, showing that Na,K-ATPase is necessary for the production of EP+. Elimination of K+ as well as Na+ from the perfusate did not change the value of the negative EP, showing that no K-ATPase is involved.

Low‐Frequency Auditory Characteristics: Species Dependence

The magnitude and phase characteristics of the sound pressure at the eardrum‐to‐cochlear microphonic potential transfer function were measured at low frequencies for four species: cat, chinchilla, guinea pig, and kangaroo rat. The former two and the latter two demonstrated radically different properties in both magnitude and phase response. It is suggested that, since at low frequencies the middle‐ear transfer functions of these four species are similar, the discrepancies are caused by differing acoustic input impedances of the cochleas that are influenced by the physical dimensions of the helicotrema and of the cochlear spiral.