Purinergic signaling in the organ of Corti: Potential therapeutic targets of sensorineural hearing losses

Brain Res Bull. 2019 Sep:151:109-118. doi: 10.1016/j.brainresbull.2019.01.029. Epub 2019 Feb 2.

Abstract

Purinergic signaling is deeply involved in the development, functions and protective mechanisms of the cochlea. Release of ATP and activation of purinergic receptors on sensory and supporting/epithelial cells play a substantial role in cochlear (patho)physiology. Both the ionotropic P2X and the metabotropic P2Y receptors are widely distributed on the inner and outer hair cells as well as on the different supporting cells in the organ of Corti and on other epithelial cells in the scala media. Among others, they are implicated in the sensitivity adjustment of the receptor cells by a K+ shunt and can attenuate the cochlear amplification by modifying cochlear micromechanics acting on outer hair cells and supporting cells. Cochlear blood flow is also regulated by purines. Sensorineural hearing losses currently lack any specific or efficient pharmacotherapy. Decreasing hearing sensitivity and increasing cochlear blood supply by pharmacological targeting of purinergic signaling in the cochlea are potential new therapeutic approaches in these hearing disabilities, especially in the noise-induced ones.

Keywords: Hearing sensitivity; Noise induced hearing loss; Organ of Corti; Purinergic signaling; Sensorineural hearing losses; Supporting cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Cochlea / metabolism
  • Cochlea / physiology
  • Hearing / physiology
  • Hearing Loss / metabolism*
  • Hearing Loss / physiopathology
  • Humans
  • Noise
  • Organ of Corti / metabolism*
  • Organ of Corti / physiology
  • Purines / metabolism
  • Receptors, Purinergic / metabolism*
  • Receptors, Purinergic / physiology
  • Receptors, Purinergic P1 / metabolism
  • Receptors, Purinergic P1 / physiology
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2 / physiology
  • Signal Transduction / drug effects

Substances

  • Purines
  • Receptors, Purinergic
  • Receptors, Purinergic P1
  • Receptors, Purinergic P2
  • Adenosine Triphosphate