Outer hair cell receptor current and sensorineural hearing loss

Basilar-membrane responses to tones at the base of the chinchilla cochlea

“…Some of our laboratory's publications noted in passing that velocity-intensity functions of chinchilla basilar-membrane responses to CF tones could approach linearity at high stimulus intensities (Ruggero and Rich, 1991b;Ruggero et al, 1992b;Ruggero et al, 1993). Such tendency toward linearization was rarely observed in Mössbauer experiments in normal cochleae (Sellick et al, 1982;Robles et al, 1986), but some authors argued for its existence on the basis of the effects of acoustic trauma (Patuzzi et al, 1984) and from theoretical considerations Johnstone et al, 1986;Patuzzi et al, 1989;Yates, 1990;Goldstein, 1995;Nobili and Mammano, 1996). The present investigation shows that within the range of intensities that are physiologically relevant (e.g., up to 100-110 dB) complete linearization does not occur in healthy cochleae.…”

“…The gain of the "cochlear amplifier"-There is widespread belief that something akin to an amplifier (Davis, 1983;Dallos, 1988Dallos, , 1992, active in healthy cochleae and presumably residing in the organ of Corti, is responsible for boosting the otherwise insensitive basilar-membrane responses of "passive" cochleae. One proposed method for measuring the gain of the cochlear amplifier is based on the presumption that responses to CF tones grow linearly at both low and high levels of stimulation (e.g., Johnstone et al, 1986;Patuzzi et al, 1989;Yates, 1990;Goldstein, 1995). The gain is defined as the difference between the sensitivities of responses to high-and low-level CF tones.…”

Normal Hearing Sensitivity at Low to Middle Frequencies with ∼25% Prestin

“…Here we created mice that expressed reduced levels of prestin (Q max ∼ 50% in neo/neo, ∼25% in neo/-), and showed reduced density of total charge movement (55% in neo/neo, 30% in neo/-) and electromotility (80% in neo/neo, 40% in neo/-). Following the mentioned model, we expected ∼25% and 50% of normal prestin activity to result in a 39.0-42.5 dB loss of amplification if we assume that wild-type cochleae achieved 45 dB of amplification (NP Cooper, personal communication; [5,17]). Surprisingly, we found that hearing sensitivity in neo/neo and neo/-mice was comparable to that of wild-type controls, leading us to conclude that (1) neuronal activity and OHC activity in vivo are not linearly correlated with prestin activity measured in vitro; and (2) ∼25% of prestin activity is sufficient for wild-type-like hearing sensitivity up to 22 kHz.…”

“…In existing models of cochlear amplification [5], the contribution of OHCs to BM vibration is seen as a simple feedback system in which the outputs (y) are related to the inputs (x) according to the equation y = x/(1 − β ), where β is the feedback efficiency. Assuming a linear correlation between the feedback efficiency and the activity of prestin (NLC and electromotility), a nonlinear correlation between NLC/electromotility and amplification gain can be predicted.…”

“…Using Patuzzi's model [5], if the amount of prestin is proportional to the degree of feedback efficiency, the gain of the amplifier should decrease nonlinearly with decreasing quantities of prestin from 100% to 0%. Prestin knockout heterozygous mice were previously used to study this relationship, however, they showed compensatory upregulation of prestin and thereby wild-type-like hearing [6].…”