Heteromultimeric P2X1/2 receptors show a novel sensitivity to extracellular pH
Heteromultimeric P2X1/2 receptors show a novel sensitivity to extracellular pH
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DOI：
10.1124/jpet.300.2.673
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发表时间：
2002-02-01
影响因子：
3.5
通讯作者：
King, BF
中科院分区：
文献类型：
--
作者：
Brown, SG;Townsend-Nicholson, A;King, BF
大鼠P2 X（1）和P2 X（2）亚基在去卵泡的非洲爪蟾卵母细胞中共表达，并在电压钳条件下研究所产生的P2 X受体。细胞外ATP引起双相内向电流，包括最初的快速失活（P2 X（1）样）成分和后来的缓慢失活（P2 X（2）样）成分。通过降低细胞外pH值（从7.5至6.5），某些细胞中P2 X（1）样ATP反应的最大幅度增加，而P2 X（2）样反应以及同型rP 2X（1）和rP 2X（2）受体的反应则不受此处理的影响。pH增强的P2 X（1）样反应的ATP浓度-反应（C/R）曲线是双相的，并且与同聚体rP 2X（1）和rP 2X（2）受体的双相ATP C/R曲线明显不同。在酸性（pH 5.5和6.5）和碱性（pH 8.5）条件下，与pH 7.5的数据相比，P2 X（1）样反应的ATP C/R曲线显示激动剂效力和效力增加，但同型rP 2X（1）和rP 2X（2）受体的情况并非如此。P2 X（2）样反应的ATP C/R曲线与同型rP 2X（2）受体的C/R曲线重叠，在所有测试的pH水平下，P2 X（2）样和P2 X（2）反应的激动剂效力和功效测定结果相同。我们的结果表明，P2 X（1）样反应具有同聚P2 X（1）受体的动力学，但酸敏感性不同于同聚P2 X（1）和P2 X（2）受体。相比之下，P2 X（2）样反应完全匹配同源P2 X（2）受体的预期特征。因此，P2 X（1）和P2 X（2）亚基的共表达产生了同源和异源P2 X受体的混合群体，其中一个新的pH敏感性P2 X受体亚群显示出可识别的独特性质，表明异源P2 X（1/2）离子通道的形成。
Rat P2X(1) and P2X(2) subunits were coexpressed in defolliculated Xenopus oocytes and the resultant P2X receptors studied under voltage-clamp conditions. Extracellular ATP elicited biphasic inward currents, involving an initial rapidly inactivating (P2X(1)-like) component and a later slowly inactivating (P2X(2)-like) component. The maximum amplitude of P2X(1)-like ATP responses was increased in some cells by lowering extracellular pH (from 7.5 to 6.5), whereas P2X(2)-like responses and those of homomeric rP2X(1) and rP2X(2) receptors were not changed by this treatment. Concentration-response (C/R) curves for ATP for pH-enhanced P2X(1)-like responses were biphasic, and clearly distinct from monophasic ATP C/R curves for homomeric rP2X(1) and rP2X(2) receptors. Under acidic (pH 5.5 and 6.5) and alkaline (pH 8.5) conditions, ATP C/R curves for P2X(1)-like responses showed increases in agonist potency and efficacy, compared with data at pH 7.5, but the same was not true of homomeric rP2X(1) and rP2X(2) receptors. ATP C/R curves for P2X(2)-like responses overlay C/R curves for homomeric rP2X(2) receptors, and determinations of agonist potency and efficacy were identical for P2X(2)-like and P2X(2) responses at all pH levels tested. Our results show that P2X(1)-like responses possessed the kinetics of homomeric P2X(1) receptors but an acid sensitivity different from homomeric P2X(1) and P2X(2) receptors. In contrast, the P2X(2)-like responses exactly matched the profile expected of homomeric P2X(2) receptors. Thus, coexpression of P2X(1) and P2X(2) subunits yielded a mixed population of homomeric and heteromeric P2X receptors, with a subpopulation of novel pH-sensitive P2X receptors showing identifiably unique properties that indicated the formation of heteromeric P2X(1/2) ion channels.