Slow Outer Hair Cell Contractions Are Essential for Fast Electrical Responses to Intense Sound.

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.