P2X receptors in cochlear Deiters' cells

Br J Pharmacol. 1998 May;124(2):337-44. doi: 10.1038/sj.bjp.0701848.

Abstract

1. The ionotropic purinoceptors in isolated Deiters' cells of guinea-pig cochlea were characterized by use of the whole-cell variant of the patch-clamp technique. 2. Extracellular application of adenosine 5'-triphosphate (ATP) induced a dose-dependent inward current when the cells were voltage-clamped at -80 mV. The ATP-induced current showed desensitization and had a reversal potential around -4 mV. 3. Increasing intracellular free Ca2+ by decreasing the concentration of EGTA in the pipette solution reduced the amplitude of the ATP-gated current. 4. The order of agonist potency was: 2-methylthioATP (2-meSATP)>ATP>benzoylbenzoyl-ATP (BzATP)>alpha,beta-methyleneATP (alpha,beta,meATP>adenosine 5'-diphosphate (ADP)>uridine 5'-triphosphate (UTP)>adenosine 5'-monophosphate (AMP)=adenosine (Ad). 5. Pretreatment with forskolin (10 microM), 8-bromoadenosine-3',5'-cyclophosphate (8-Br-cyclic AMP, 1 mM), 3-isobutyl-1-methylxanthine (IBMX, 1 mM) or phorbol-12-myristate-13-acetate (PMA, 1 microM) reversibly reduced the ATP-induced peak current. 6. The results are consistent with molecular biological data which indicate that P2X2 purinoceptors are present in Deiters' cells. In addition, the reduction of the ATP-gated current by activators of protein kinase A and protein kinase C indicates that these P2X2 purinoceptors can be functionally modulated by receptor phosphorylation.

Publication types

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

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenosine / pharmacology
  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Calcium / metabolism
  • Cochlea / drug effects
  • Cochlea / metabolism*
  • Colforsin / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Guinea Pigs
  • Patch-Clamp Techniques
  • Protein Kinases / metabolism*
  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2 / physiology*
  • Receptors, Purinergic P2X2
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thionucleotides / pharmacology
  • Uridine Triphosphate / pharmacology
  • Vasodilator Agents / pharmacology
  • Vestibular Nucleus, Lateral / drug effects
  • Vestibular Nucleus, Lateral / metabolism*

Substances

  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X2
  • Thionucleotides
  • Vasodilator Agents
  • Colforsin
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Protein Kinases
  • Adenosine
  • Tetradecanoylphorbol Acetate
  • alpha,beta-methyleneadenosine 5'-triphosphate
  • Calcium
  • 1-Methyl-3-isobutylxanthine
  • Uridine Triphosphate
  • 2-methylthio-ATP