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

Sahlin Pettersen, H.; Fridberger, A.; Hakizimana, P.

2025-04-27 neuroscience
10.1101/2025.04.24.650391 bioRxiv
Show abstract

The cochlea protects itself from intense sound via slow mechanical contractions, but the real-time kinetics linking this process to the stimulus-evoked electrical potentials have remained unresolved. Here, using high-speed confocal imaging with AI-driven analysis, we synchronously measured organ of Corti mechanics and stimulus-evoked potentials in the living isolated guinea pig cochlea. We discovered an inverse kinetic relationship: the outer hair cells (OHC) slow, somatic contraction is essential for generating a fast electrical response. Pharmacologically blocking the OHC motor protein prestin inverted this dynamic; the OHCs mechanical contraction became faster, while the normally rapid electrical potential became nearly ten times slower. These findings indicate that slow OHC motility is not merely a byproduct of overstimulation but a control mechanism. It functions to regulate and sharpen the kinetics of the stimulus-evoked potential, providing a cellular-level explanation for how the hearing organ protects itself while maintaining temporal fidelity during intense sound exposure.

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