Molecular cloning, functional characterization and possible cooperativity between the murine P2X₄ and P2X_4a receptors

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• 作者：Townsend-Nicholson ; Andrea ; King ; Brian F. ; Wildman ; Scott S. ; Burnstock ; Geoffrey
• 关键词：P2X receptor ; P2X₄ ; Ion channel ; Alternative splicing ; ATP ; Oocyte
• 刊名：Molecular Brain Research
• 出版年：1999
• 出版时间：February 5, 1999
• 年：1999
• 卷：64
• 期：2
• 页码：246-254
• 全文大小：464 K

文摘

We have cloned and functionally characterised the mouse orthologue of the P2X₄ receptor, mP2X₄, and a splice variant of this receptor, mP2X_4a. mP2X₄ is 388 amino acids in length and shares 94 % and 87 % identity with the rat and human P2X₄ receptors, respectively, while mP2X_4a is 361 amino acids in length and lacks a 27-amino acid region in the extracellular domain corresponding to exon 6 of the known P2X receptor gene structures. When expressed in Xenopus laevis oocytes, mP2X₄ produces a rapid inward current in response to ATP with an EC₅₀ of 1.68±0.2 μM, consistent with the affinity of the rat and human P2X₄ receptors for ATP. This agonist response is potentiated by the P2X receptor antagonists suramin, Reactive blue 2 and, over a limited concentration range, by PPADS. Although mP2X_4a forms a poorly functional homomeric receptor, it appears able to interact with the full-length mP2X₄ subunit to result in a functional channel with a reduced affinity for ATP. These results suggest a possible role for splice variants of P2X receptors in the formation of functional heteromeric ion channels.