Shen Jian-Bing, Pappano Achilles J, Liang Bruce T
Pat and Jim Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
FASEB J. 2006 Feb;20(2):277-84. doi: 10.1096/fj.05-4749com.
P2X receptors, activated by extracellular ATP, may be important in regulating cardiac function. The objective of the present study was to characterize the electrophysiologic actions of P2X4 receptors in cardiac myocytes and to determine whether they are involved in mediating the effect of extracellular ATP. Membrane currents under voltage clamp were determined in myocytes from both wild-type (WT) and P2X4 receptor-overexpressing transgenic (TG) mice. The P2X agonist 2-meSATP induced an inward current at -100 mV that was greater in magnitude (2-fold) in TG than in WT ventricular cells. In the presence of the P2X4 receptor-selective allosteric enhancer ivermectin (3 microM), the 2-meSATP-stimulated current increased significantly in both WT and TG ventricular cells, consistent with an important role of P2X4 receptors in mediating the ATP current not only in TG but also WT myocytes. That the current in both WT and TG cells showed similar voltage-dependence and reverse potential (approximately 0 mV) further suggests a role for this receptor in the normal electrophysiological action of ATP in WT murine cardiac myocytes. The P2X antagonist suramin was only able to block partially the 2-meSATP-stimulated current in WT cells, implying that both P2X4 receptor and another yet-to-be-identified P2X receptor mediate this current.
由细胞外ATP激活的P2X受体可能在调节心脏功能方面发挥重要作用。本研究的目的是表征心肌细胞中P2X4受体的电生理作用，并确定它们是否参与介导细胞外ATP的效应。在野生型（WT）和过表达P2X4受体的转基因（TG）小鼠的心肌细胞中测定电压钳下的膜电流。P2X激动剂2-甲硫基ATP（2-meSATP）在-100 mV时诱导内向电流，其幅度在TG心室细胞中比WT心室细胞大（2倍）。在存在P2X4受体选择性变构增强剂伊维菌素（3 microM）的情况下，2-meSATP刺激的电流在WT和TG心室细胞中均显著增加，这与P2X4受体不仅在TG而且在WT心肌细胞中介导ATP电流的重要作用一致。WT和TG细胞中的电流显示出相似的电压依赖性和反转电位（约0 mV），这进一步表明该受体在WT小鼠心肌细胞中ATP的正常电生理作用中发挥作用。P2X拮抗剂苏拉明仅能部分阻断WT细胞中2-meSATP刺激的电流，这意味着P2X4受体和另一种尚未确定的P2X受体均介导该电流。
