title: ATP activates P2X receptors to mediate gap junctional coupling in the cochlea.
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 Ca(2+) influxing, thereby increasing intracellular Ca(2+) 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.
authors.affiliation: Dept. of Otolaryngology, University of Kentucky Medical Center, Lexington, KY 40536 0293, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Zhao
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003051:Cochlea / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D058469:Receptors, Purinergic P2X / Q000378:metabolism / Q000502:physiology*; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D058469:Receptors, Purinergic P2X; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate