P2X receptors in cochlear Deiters' cells.
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.
Chen
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Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans 70112-2234, USA.
Bobbin
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D018408:Patch-Clamp Techniques; D011494:Protein Kinases / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058476:Receptors, Purinergic P2X2; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D003689:Vestibular Nucleus, Lateral / Q000187:drug effects / Q000378:metabolism*
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D013873:Thionucleotides; D014665:Vasodilator Agents; D005576:Colforsin; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D014544:Uridine Triphosphate; C008501:2-methylthio-ATP