Prestin and OHC Electromotility
TL;DR: Prestin is the molecular motor in outer hair cells (OHCs) that converts electrical signals to mechanical length changes at microsecond timescales. It is the effector of the cochlear amplifier. In STRC-loss hearing loss, prestin still works — the amplifier hardware is intact but disconnected from its sensor.
What Prestin Does
Prestin (SLC26A5) is a voltage-sensitive motor protein in the lateral wall of OHCs. When the intracellular voltage changes (due to stereocilia-driven ion currents), prestin molecules change shape, causing the OHC to shorten or elongate by ~4% at speeds up to 80,000 Hz.
This electromotility is what makes active cochlear amplification possible:
- Sound → basilar membrane vibration → stereocilia deflect
- Mechanotransduction channels open → K⁺/Ca²⁺ influx → voltage change
- Prestin activates → OHC length change → mechanical feedback to basilar membrane
- Net result: up to 60 dB amplification of incoming sound
This loop operates at acoustic frequencies (kHz) — prestin’s speed is the enabling constraint.
The STRC Connection
In STRC-loss hearing (Misha), the prestin-motor is functionally intact. What breaks is step 1: stereocilia tips lose coupling to the tectorial membrane (stereocilin anchors that coupling). The transduction signal never reaches prestin.
This is why STRC is considered highly repairable by gene therapy: the amplifier effector (prestin) does not need to be replaced. Restoring stereocilin via AAV restores the input signal; prestin does the rest.
If both STRC and prestin were broken (as in cisplatin ototoxicity), the OHCs would need complete replacement.
Relation to Hopf Dynamics
The OHC feedback loop (stereocilia → prestin → basilar membrane → stereocilia) forms a Hopf oscillator. Prestin’s electromotility is the amplification element that allows this loop to sit near the bifurcation point. Without prestin, the loop gain drops to zero: no active tuning, no bifurcation dynamics, no cochlear amplifier.
Near-criticality gives the cochlea:
- Maximum sensitivity (gain diverges at the bifurcation point)
- Sharp frequency tuning (nonlinear saturation creates narrow bandpass)
- Amplification of slow AM signals in the 0.5-5 Hz window (see Convergent Therapeutic Frequency Window)
Prestin as OHC-Specific Marker
Because prestin is expressed almost exclusively in OHCs, it is used as a targeting handle in experimental drug delivery:
- Antibody-decorated exosomes targeting prestin on OHC surfaces
- In vivo electroporation guidance to OHC populations
- Distinction from IHC populations in surgical delivery planning
See Alternative STRC Delivery Hypotheses.
Zhao 2025: Enhancer-Driven Prestin Restoration
Zhao et al. (2025) identified cochlear enhancer B8 that drives Slc26a5 (prestin) expression specifically in OHCs. Enhancer-guided gene therapy restored hearing sensitivity in prestin-knockout mice. This confirms that prestin expression can be tissue-specifically controlled — relevant for STRC gene therapy vectors that need OHC specificity.
Connections
[part-of]Cochlear Amplifier as Hopf Oscillator — prestin is the electromechanical effector of the Hopf oscillator- STRC Hearing Loss — input disconnected, effector intact
- Alternative STRC Delivery Hypotheses — OHC-specific targeting via prestin surface markers
[see-also]Closed-Loop Sound Therapy — electromotility loop is an inherently closed-loop system[see-also]Activity-Dependent Closed-Loop Therapy — OHC electromotility provides feedback channel[see-also]Convergent Therapeutic Frequency Window — near-critical OHC gain amplifies 0.5-5 Hz AM[about]Misha[part-of]STRC Gene Therapy Landscape 2026[part-of]Acoustics[part-of]MOC - Audio & DSP[part-of]MOC - Psychology & ADHD