Scientists find new way to protect hearing from loud noise damage
Researchers identified how a chemical messenger in the inner ear shields against hearing loss during noise exposure, opening a path for preventive treatments. The finding could lead to therapies for workers, military personnel, and others at risk of noise-induced deafness—a condition affecting hundreds of millions globally.
Originaltitel: Perilymphatic ATP plays a critical role in modulating cochlear function to protect from loud sound induced hearing loss.
Perilymfatisk ATP kan förhindra bullerstörd hörselnedsättning genom en tidigare okänd signalväg i innerörat. Linköpings universitet identifierade att ATP i perilymfvätskan—inte endolymfvätskan—aktiverar P2X2-receptorer på Reissner's membran och hårceller, vilket minskar ljudinducerade elektriska potentialer från 486 μV till 315 μV vid 80 dB SPL. Mikroskopi och elektronfysiologi visade även reducerad rörelse i yttre hårcellsstereocilier (135 nm till 99 nm) och Hensels celler (128 nm till 101 nm). Effekterna var reversibla vid ATP-borttagning och förknippades med minskad intracellulär kalcium. Denna perilymfspecifika mekanism skiljer sig från den klassiska kationshuntmodellen. För leverantörer av hörselvård och audiologiska innovatörer öppnar upptäckten vägen för nya terapeutiska interventioner mot bullerskador—ett område utan effektiva preventivbehandlingar idag.
BACKGROUND: Extracellular adenosine triphosphate (ATP) signalling via purinergic receptors plays a key role in cochlear adaptation to loud sound. Traditionally, ATP activation of purinergic receptor P2X receptors has been proposed to induce a cation shunt, reducing the endolymphatic potential and the driving force for sound transduction. However, direct evidence for this protective mechanism remains limited. Here, we provide direct experimental evidence identifying a distinct, compartment-specific ATP signalling pathway that modulates cochlear function. METHODS: In mature Dunkin-Hartley guinea pigs of either sex, we combined time-resolved confocal microscopy, electrophysiology, live-cell imaging, and fluorescence spectroscopy to characterise how compartmentalised extracellular ATP regulates cochlear function during moderate loud sound exposure. FINDINGS: ATP delivered to the perilymphatic space where P2X2 receptors localised in Reissner's membrane epithelial cells, supporting cells, and hair cells significantly reduced sound-evoked electrical potentials from 486 μV to 315 μV, outer hair cell stereocilia motion from 135 nm to 99 nm and Hensen's cell motion from 128 nm to 101 nm at 80 dB SPL. These effects were reversible upon ATP removal and accompanied by decreased intracellular calcium. In contrast, ATP applied to the endolymph produced no comparable changes. These findings demonstrate that extracellular ATP in the perilymph protects the cochlea from high-intensity sound through a mechanism distinct from the classical cation shunt model. INTERPRETATION: These findings reveal a previously unrecognised perilymph-driven ATP signalling pathway that extend beyond the traditional P2X-mediated cation shunt, demonstrating that extracellular ATP plays a critical role in protecting the cochlea mainly from loud sound-induced hearing loss. FUNDING: Swedish Research Council 2017-06092 and 2022-00548.