Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway.
Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway.
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酸性 ATP 通过一种新途径激活淋巴细胞向外调整氯离子通道。
DOI：
10.1007/s00424-004-1305-2
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Warnock,DavidG
中科院分区：
文献类型：
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作者：
Ma,He-Ping;Zhou,Zhen-Hong;Liang,You-You;Saxena,Sunil;Warnock,DavidG
利用全细胞膜片钳技术，我们发现ATP激活的外向整流电流在Daudi人B淋巴瘤细胞在酸性条件下。用Cl-取代葡萄糖酸盐-改变了逆转电位，而Cl-通道阻滞剂4，4 '-二异硫氰基二苯乙烯-2，2'-二磺酸（DIDS）和9-蒽羧酸（9-AC）则阻断了电流，这表明ATP通过激活外向整流氯离子通道（ORCC）来诱导该电流。ATP对ORCC的作用可被ADP模拟，但不能被其他P2受体激动剂如ATPγS（ATP的难水解类似物）、2 '，3'-O-苯甲酰基-4-苯甲酰基-ATP（BzATP）和UTP模拟。100 μM的P2受体拮抗剂苏拉明（suramin）可完全阻断ATP诱导的ORCC电流，而100 μM的P2受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸四磺酸钠（PPADS）可部分阻断ATP诱导的ORCC电流。G蛋白的失活和细胞外Ca ~（2+）的消除均不影响ATP诱导电流，表明G蛋白偶联的P2 Y受体和Ca ~（2+）可渗透的P2 X受体不参与ATP诱导电流。基于药理学特征和ATP激活ORCC所需的酸性条件的事实，我们建议酸性ATP通过一种新的途径激活淋巴细胞ORCC，该途径与任何先前描述的嘌呤能受体无关。
Using whole-cell patch-clamp techniques we found that ATP activated an outwardly rectifying current in Daudi human B lymphoma cells under acidic conditions. The substitution of Cl−for gluconate−shifted the reversal potential, while Cl−channel blockers, 4,4’-diisothiocyanostibene-2,2’-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC), blocked the current, indicating that ATP induces this current by activating the outwardly rectifying chloride channel (ORCC). The effect of ATP on ORCC was mimicked by ADP, but not by other P2 receptor agonists such as ATPγS (a poorly hydrolyzable analog of ATP), 2’,3’-O-benzoyl-4-benzoyl-ATP (BzATP), and UTP. The ATP-induced ORCC current was completely blocked by 100 μM suramin (a P2 receptor antagonist), and was partially blocked by 100 μM pyridoxal-phosphate-6-azophenyl-2’,4’-disulfonic acid tetrasodium (PPADS), which is another P2 receptor antagonist. Neither inactivation of G proteins nor elimination of extracellular Ca2+affected the ATP-induced current, indicating that G protein-coupled P2Y receptors and Ca2+-permeable P2X receptors are not involved. Based on the pharmacological profile and the fact that acidic conditions are required for ATP to activate the ORCC, we suggest that acidic ATP activates the lymphocyte ORCC via a novel pathway, which is not associated with any previously described purinergic receptors.