Unique functional properties of a sensory neuronal P2X ATP-gated channel from zebrafish.
We report here the structural and functional characterization of an ionotropic P2X ATP receptor from the lower vertebrate zebrafish (Danio rerio). The full-length cDNA encodes a 410-amino acid-long channel subunit zP2X(3), which shares only 54% identity with closest mammalian P2X subunits. When expressed in Xenopus oocytes in homomeric form, ATP-gated zP2X(3) channels evoked a unique nonselective cationic current with faster rise time, faster kinetics of desensitization, and slower recovery than any other known P2X channel. Interestingly, the order of agonist potency for this P2X receptor was found similar to that of distantly related P2X(7) receptors, with benzoylbenzoyl ATP (EC(50) = 5 microM) >> ATP (EC(50) = 350 microM) = ADP > alpha,beta-methylene ATP (EC(50) = 480 microM). zP2X(3) receptors are highly sensitive to blockade by the antagonist trinitrophenyl ATP (IC(50) < 5 nM) but are weakly sensitive to the noncompetitive antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid. zP2X(3) subunit mRNA is exclusively expressed at high levels in trigeminal neurons and Rohon-Beard cells during embryonic development, suggesting that neuronal P2X receptors mediating fast ATP responses were selected early in the vertebrate phylogeny to play an important role in sensory pathways.
Boué-Grabot
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Cell Biology of Excitable Tissue Research Group, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Akimenko
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Séguéla
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D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017403:In Situ Hybridization; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000378:metabolism; D009928:Organ Specificity; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014982:Xenopus laevis; D015027:Zebrafish; D029961:Zebrafish Proteins
D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D029961:Zebrafish Proteins; C413926:p2rx3a protein, zebrafish; D000255:Adenosine Triphosphate