Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia
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Mouse parotid acinar cells express P2X4 and P2X7 receptors (mP2X4R and mP2X7R) whose physiological function remains undetermined. Here we show that mP2X4R expressed in HEK-293 cells do not allow the passage of tetraethylammonium (TEA%2b) and promote little, if any, ethidium bromide (EtBr) uptake when stimulated with ATP or BzATP. In contrast, mP2X7R generates slowly decaying TEA%2b current, sustained Na%2b current and promotes robust EtBr uptake. However, ATP-activated TEA%2b current from acinar cells was unlike that generated by mP2X7R or mP2X4R. Functional interactions between mP2X4R and mP2X7R were investigated in HEK cells co-transfected with different mP2X4:mP2X7 cDNA ratios and using solutions containing either TEA%2b or Na%2b ions. Co-expressed channels generated a TEA%2b current that displayed faster decay during ATP stimulation than mP2X7R alone. Moreover, cells transfected with a 2:1 cDNA ratio displayed decaying kinetics similar to those observed in acinar cells. Concentration-response curves in Na%2b-containing solutions were constructed for heterologously expressed mP2X4R, mP2X7R and mP2X4 R:mP2X7R co-expressions as well as acinar cells. The EC50 values determined were 11, 220, 434 and 442 μm, respectively. Na%2b currents generated by expressing mP2X4R or mP2X7R alone were potentiated by ivermectin (IVM). In contrast, IVM potentiation in acinar cells and HEK cells co-expressing P2X4 and P2X7 (1:1 or 2:1 cDNA ratios) was seen only when the ATP concentration was lowered from 5 to 0.03mm. Taken together our observations indicate a functional interaction between murine P2X7 and P2X4 receptors. Such interaction might occur in acinar cells to shape the response to extracellular ATP in salivary epithelia. © 2009 The Authors. Journal compilation © 2009 The Physiological Society.
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adenosine triphosphate; complementary DNA; ethidium bromide; ivermectin; purinergic P2X4 receptor; purinergic P2X7 receptor; sodium ion; tetrylammonium; purinergic P2X4 receptor; purinergic P2X7 receptor; sodium; adenosine triphosphate; ethidium; fluorescent dye; ivermectin; purinergic P2 receptor; purinergic P2X4 receptor; purinergic P2X7 receptor; sodium channel; acinar cell; animal cell; article; cell membrane permeability; cell strain HEK293; cell transport; concentration response; controlled study; epithelium cell; genetic transfection; heterologous expression; human; human cell; mouse; nonhuman; priority journal; protein expression; protein protein interaction; saliva; sodium current; Article; EC50; HEK293 cell line; ion permeability; animal; cell line; cytology; drug potentiation; electrophysiology; epithelium; metabolism; parotid gland; patch clamp; physiology; salivary gland; statistical analysis; Adenosine Triphosphate; Animals; Cell Line; Data Interpretation, Statistical; Electrophysiology; Epithelium; Ethidium; Fluorescent Dyes; Humans; Ivermectin; Mice; Parotid Gland; Patch-Clamp Techniques; Receptors, Purinergic P2; Salivary Glands; Sodium Channels; Transfection
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