Unique functional properties of a sensory neuronal P2X ATP-gated channel from zebrafish
Unique functional properties of a sensory neuronal P2X ATP-gated channel from zebrafish
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DOI：
10.1046/j.1471-4159.2000.0751600.x
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发表时间：
2000-10-01
影响因子：
4.7
通讯作者：
Séguéla, P
中科院分区：
文献类型：
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作者：
Boué-Grabot, E;Akimenko, MA;Séguéla, P
我们在这里报告的结构和功能特性的离子型P2 X ATP受体从较低的脊椎动物斑马鱼（Danio rerio）。全长cDNA编码一个410个氨基酸长的通道亚基zP 2X（3），它与最接近的哺乳动物P2 X亚基只有54%的同一性。当以同源形式在非洲爪蟾卵母细胞中表达时，ATP门控zP 2X（3）通道诱发了一种独特的非选择性阳离子电流，具有比任何其他已知的P2 X通道更快的上升时间、更快的脱敏动力学和更慢的恢复。有趣的是，发现这种P2 X受体的激动剂效力的顺序与远亲P2 X受体相似，苯甲酰苯甲酰基ATP（EC 50 = 5 μ M）比ATP（EC 50 = 350 μ M）大得多= ADP > α，β-亚甲基ATP（EC 50 = 480 μ M）。zP 2X（3）受体对拮抗剂三硝基苯基ATP的阻断高度敏感（IC 50 < 5 nM），但对非竞争性拮抗剂磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸的敏感性较弱。zP 2X（3）亚基mRNA在胚胎发育过程中仅在三叉神经元和Rohon-Beard细胞中高水平表达，这表明在脊椎动物胚胎发育早期，介导快速ATP反应的神经元P2 X受体在感觉通路中起重要作用。
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, receptors, with benzoylbenzoyl ATP (EC50 = 5 mu M) much greater than ATP (EC50 = 350 mu M) = ADP > alpha,beta-methylene ATP (EC50 = 480 mu M). zP2X(3) receptors are highly sensitive to blockade by the antagonist trinitrophenyl ATP (IC50 < 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.