ATP activates P2X receptors to mediate gap junctional coupling in the cochlea

Yan Zhu, Hong Bo Zhao

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

ATP is an important extracellular signaling molecule and can activate both ionotropic (P2X) and metabotropic purinergic (P2Y) receptors to influence cellular function in many aspects. Gap junction is an intercellular channel and plays a critical role in hearing. Here, we report that stimulation of ATP reduced gap junctional coupling between cochlear supporting cells. This uncoupling effect could be evoked by nanomolar physiological levels of ATP. A P2X receptor agonist benzoylbenzoyl-ATP (BzATP) but not a P2Y receptor agonist UTP stimulated this uncoupling effect. Application of P2X receptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 50μM) or oxidized ATP (oATP, 0.1mM) eliminated this uncoupling effect. We further found that ATP activated P2X receptors in the cochlear supporting cells allowing Ca2+ influxing, thereby increasing intracellular Ca2+ concentration to mediate gap junctions. These data suggest that ATP can mediate cochlear gap junctions at the physiological level by the activation of P2X receptors rather than P2Y receptors. This P2X receptor-mediated purinergic control on the cochlear gap junctions may play an important role in the regulation of K+-recycling for ionic homeostasis in the cochlea and the reduction of hearing sensitivity under noise stress for protection.

Original languageEnglish
Pages (from-to)528-532
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume426
Issue number4
DOIs
StatePublished - Oct 5 2012

Bibliographical note

Funding Information:
This work was supported by NIH R01 DC 05989 .

Keywords

  • ATP
  • Gap junction
  • Inner ear
  • Potassium
  • Purinergic receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'ATP activates P2X receptors to mediate gap junctional coupling in the cochlea'. Together they form a unique fingerprint.

Cite this