Slow Mechanical Filtering by Outer Hair Cells Enhances Rather than Limits Receptor Potential Kinetics

Mammals achieve extraordinarily sensitive hearing through the active amplification of sound vibrations in the cochlea. Central to this process is the electromotility of outer hair cells (OHCs)—their somatic length changes powered by the membrane motor protein prestin, which converts receptor potentials into mechanical forces.

Yet the intrinsic RC (resistance–capacitance) low-pass filtering of the OHC membrane poses a paradox: how can OHCs generate the rapid force changes necessary for effective amplification? One hypothesis suggests that hair bundle adaptation, operating on sub-to tens-of-millisecond timescales, might compensate for the comparatively slower somatic response.

In this study, we resolve the paradox by simultaneously recording sound-evoked electrical and mechanical responses in the guinea pig cochlear apex during adaptation-inducing intense sound stimulation. High-speed confocal microscopy paired with AI-based segmentation enabled two-dimensional quantification of the OHC mechanical response—tracking changes in length, width, and area—while extracellular recordings captured receptor potentials.

Under control conditions, the inherently slow kinetics of prestin-mediated mechanical changes serve to sharpen receptor potential kinetics. Notably, pharmacological blockade of prestin with salicylate reversed this relationship: the mechanical response kinetics became markedly sharper, while receptor potential kinetics shifted into a sluggish, low-pass regime.

These findings demonstrate that the intrinsic low-pass filtering of electromotility is not a limitation but rather a critical feature that preserves rapid electrical transduction, thereby underpinning the exquisite sensitivity of the mammalian auditory system.

Significance Statement

Understanding the mechanisms underlying cochlear amplification is central to deciphering the exquisite sensitivity of mammalian hearing. Our study reveals a reciprocal interplay between mechanical and electrical filtering in outer hair cells. Specifically, we demonstrate that the intrinsic low-pass filtering of OHC electromotility is essential for sharpening receptor potential kinetics. When prestin is pharmacologically blocked, the mechanical response kinetics become markedly sharper while receptor potential kinetics become low-pass filtered —thereby reversing the normal interplay. By combining high-speed confocal imaging with AI-based segmentation and extracellular recordings in the guinea pig cochlear apex, our findings resolve a longstanding paradox in auditory biophysics. These insights significantly deepen our understanding of cochlear amplification and may inform novel therapeutic strategies for hearing impairments.