Extracellular ATP-stimulated current in wild-type and P2X4 receptor transgenic mouse ventricular myocytes:: implications for a cardiac physiologic role of P2X4 receptors

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 P2X(4) 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 P2X(4) 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 P2X(4) receptor-selective allosteric enhancer ivermectin (3 mu M), the 2-meSATP-stimulated current increased significantly in both WT and TG ventricular cells, consistent with an important role of P2X(4) 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 (similar to 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 P2X(4) receptor and another yet-to-be-identified P2X receptor mediate this current.